REGENXBIO Inc. (RGNX) Earnings Call Transcript & Summary

All right. Great. Hey, everyone. Good afternoon, and welcome to Day 3 of our Napa Biopharma Conference. Thanks for joining this session with REGENXBIO. My name is Alec Stranahan, I'm an analyst spearhead. I'm on the U.S. Biopharma team at BofA, and I'm also joined by Geoff Meacham, who is the senior U.S. biopharma analyst at Bank of America. And we're also pleased to have Ken Mills, President and Chief Executive Officer; as well as Steve Pakola, Chief Medical Officer of REGENXBIO on the line as well. Ken and Steve, thanks for joining us.

Thanks for having us, Alec.

Perfect. So lots to go through, so maybe we'll just jump straight into Q&A. I have a few here, but for those dialed into the webcast, if you do have questions, feel free to log them via the platform or shoot them over via e-mail. So Ken, maybe just to start, you guys had your 1Q call recently, but maybe if you wanted, in a minute or 2, just to give a status update on 314 and your other programs that are going to the clinic.

Absolutely. And thanks again to you guys and everyone who's helped and organized this event. We appreciate the participation in these tough times. And certainly, 2021 has been challenging, but also off to a great start for REGENXBIO. We continue to really define ourselves as a company that is making meaningful strides to deliver potentially curative gene therapies to patients and 1 that's involved in many different active clinical trials, research and expansion of capabilities this year. Our recent updates, Alec, were focused on continuation of our first pivotal phase program using our AAV gene therapy technology platform in treatment of wet age-related macular degeneration. And we announced early in -- really right at the end of 2020 and coming into 2021 that we were going to be moving into pivotal phase there. It's an important milestone for this onetime gene therapy in wet AMD, it really distinguishes us that the important features of the science, of the clinical work that we've evaluated of this candidate and emphasize that with support of regulators as part of our plan and capabilities to support moving into pivotal phase, we're starting to prepare for pre-commercial and commercial readiness. At the same time, we've been exploring further the pharmacology of our lead product candidate, in wet AMD and in diabetic retinopathy with another route of administration that we call suprachoroidal delivery. Those studies started last year and continue. We've updated on enrollment and expansion of trials, and I'm sure we'll get into more details there. But it's been a great exercise in execution, moving in the pivotal phase and bringing a brand-new first-time route of administration forward scientifically and clinically for a very important unmet need in wet age-related macular degeneration and related diseases. Additionally, we have an important focus in our pipeline on rare diseases, rare disease science and clinical advancement. We've been continuing across this year to tell an encouraging story that we think about our treatment for Hunter syndrome and Hurler syndrome. These are direct to CNS treatments for neurodegenerative components of really well-characterized congenital diseases, lysosomal storage programs. We've announced also that in the middle of this year, we'll be working on filing an IND in Duchenne muscular dystrophy. So very, very active time for us as a company. We're seeing a lot of expansion in the clinic. We're seeing a lot of expansion in our research labs and literal expansion in terms of facilities and capabilities just within the last month, we've actually moved into a new headquarters that houses both our research, development, general administrative office capabilities, but also we're completing the build-out of a new commercial-ready scale GMP facility, all in the same building. So we're excited about those milestones. But most importantly, we're focused on execution of our mission for patients.

All right. Great. Well, maybe just to start then, on 314. You've got your 2 pivotal studies. One is dosing patients and the other is preparing to launch. So I guess how are these going? And how has enrollment been in ATMOSPHERE so far?

Hey Alec, I can chime in here. As Ken mentioned, we're pretty excited about how far we've gotten, even in these difficult times with the pandemic. So with our first pivotal study for our subretinal program, we announced earlier this year that we kicked off that first of the 2 pivotal studies. And I have to say, we're excited. Our investigators are excited. So we're in that typical ramp-up stage of the first of the 2 pivotal studies, and that's going well. And as we previously announced, we plan to start the second of the 2 pivotal studies in the second half of this year. And it's really an exciting time for us, but also the gene therapy and the retina gene therapy space because these are -- this is the largest program ever for addressing a common disease in the retina space. So it's really been exciting with the interactions with our investigators individually and also even in a group setting, kicking off our overall pivotal program. So exciting year on that front as well as the suprachoroidal delivery program. So I'm excited to answer any questions you guys have on our wet AMD or DR program.

Perfect. And Steve, I guess, when you've been speaking with physicians and when you sort of think about the regulatory path in the future, obviously, 1 study is against Lucentis and the other is against EYLEA. I guess which of these studies do you see as being maybe the more meaningful, in terms of the clinical adoption? Or is it really going to be a combination of the 2 that really drives the overall clinical profile?

Yes. It's a great question, Alec. [Audio Gap] our cake and eating it too, because these are clearly the 2 most validated and referenced clinical programs that exist for treatment of wet AMD. Obviously, there are other agents that have come along such as off-label Avastin bevacizumab and some newer programs. But what is exciting here for us is that we have the opportunity to show how RGX-314 onetime treatment works in comparison to these 2 gold standards. So to the question of which 1 is more important, it really is the totality of it, because each has its own pros and cons. Certainly, the EYLEA has been very well adapted because of, largely in part, the lower frequency of dosing after the loading doses. But monthly Lucentis, with all of the data that exists short term and long term, both in terms of clinical trial, strict regimens of monthly dosing and other regimens, we really get to take advantage of all this historical data to both design our study and power our study with the competence of what's come before us. And I think the overarching message that we hear and one of the reasons we're excited is that whether it's against Lucentis or EYLEA, keep in mind, this is noninferiority to either of these agents in a strict clinical trial setting. And we know and all of the retina community knows, that if you can show noninferiority in that strict setting, that really translates into actual superiority in the real world, because we know patients are simply not getting close to the number of injections that they need to be getting to stave off vision loss.

Right. And we also hosted Roche at Napa this year, and they did reiterate their confidence in faricimab as being a compelling option versus Regeneron's EYLEA. So I'd be interested to hear what your view is on this asset and other, maybe emerging -- I'm thinking about the Lucentis PDS, something like that. And do you think not including faricimab as an active comparator could affect things down the road, or not really?

Well, I think programs like faricimab and other more traditional anti-VEGF mechanism, but increased durability plays, all speak to how big this unmet need is, where these patients are simply not able to have sustainable anti-VEGF for their disease. So I think all of these programs are actually validation for what we're trying to do with a onetime foundational treatment. I think these are great advances. So having worked in this space for a couple of decades and actually, in a former life, having worked on the Type 2 pathway, I'm very glad to see the advances that have been made with faricimab. For example, with the Ang-2 inhibition approach really I think, clinically validating that mechanism as an additional mechanism. And it does seem to, I think the results so far from wet AMD and DR DME specifically, to date have been very encouraging. Though it still is very much this incremental advancement in terms of durability, where we're seeing a lot of excitement for faricimab and other programs like PDS, where you can move from every 2- to 3-month dosing in a majority of patients to potentially every 4, 5 or even 6 months, in the case of PDS. But again, all of this just further validates how much of a desire there is to have a more sustainable treatment option that these incremental advances are being appropriately valued as they are. But this just further increases the enthusiasm that we hear from the retina community, if you could have a onetime treatment option that would give you a foundational amount of anti-VEGF activity that not only addresses the treatment burden aspect, but also may give an advantage in terms of efficacy because you no longer are relying on the traditional peak and trough value levels of whatever agent you might be giving, whether it's faricimab, with the dual mechanism or other traditional anti-VEGFs, that just last longer, depending on the platform that's being used. So yes, I guess in short, these are great advances, but only make us more excited for the opportunity for a onetime treatment option.

Okay guys, this is Geoff. Just to follow up on that, Steve. And then maybe for Ken, when you think about the cost benefit and the value of 314. What would you say are the inputs for how you're thinking about the cost per therapy? Is it durability of effect? Is it the duration? Is it efficacy? Is it higher visual acuity? Is it better safety? I know some of your comps to, to today are branded, but down the road, they may be biosimilars. So there's a lot of different things to kind of consider when you try to factor in like what the cost benefit is.

Yes, Geoff, that's a great point. I think that we -- when we started this program years ago, we saw the potential evolution of all of these things that we're entering the clinic or advancing even on the biosimilars front. So we -- I feel like our commercial team and our clinical team actually installed a pretty multivariable model for how to consider where gene therapy would fit in. And we've continued to use that model with data reading out against these different programs that Alec and Steve have been alluding to it. It is a combination of factors, right? Like you're talking about, I mean there's the drug cost factor, there's the convenience and compliance factor. There's the durability of gene therapy factor. I think the biggest overall impact that we see that's important in the implementation of our clinical program and the commercial plan we have for RGX-314 is about safety. and long-term durability, right? I mean I think we see a lot of these new treatments and including potential references to biosimilars. That's coming into the existing market, the same market of incidence-driven new diagnoses and short-term chronic care. But what we had taken inventory of and I think what the docs are really clamoring for, as are the patients are, what's the long-term solution for these patients? And I think, especially when you stratify the market on the basis of wet AMD or extend to areas like anti-VEGF indications in diabetes, it's a huge emerging prevalent population of people that really can't tolerate being injected into their eyeballs for years, for a variety of reasons. And we're a onetime solution with durable, consistent results that, according to our assessments that are noninferior to already what are really good restorative gains from the existing therapies, is what's needed and necessary. And so when you've looked even at our first program work with RGX-314, we've been following patients in our clinically relevant range out over 3 years in long-term follow-up studies and have shown that durability, have shown that sort of responsiveness to that onetime treatment. And we've continued to sort of consider that while we want to move forward with something that's acceptable to regulators, on as accelerated a pathway as possible for approval. We're going to be emphasizing in the market and with payers that the durability of gene therapy at a onetime treatment is a real thing and that there is meaningful value to be ascribed to that. In addition to the fact that -- and I know that you know well, and I'm sure a lot of the audience knows well, when gene therapies have a reputation of being right now, the few that are marketed, hundreds of thousands, millions of dollar level treatments in some cases. And we know that we're not heading into a market like that. And frankly, the exercise for us at REGENX is very ambitious and I think very thoughtful about wanting to take gene therapy to a market that is about treating millions of people, not necessarily some of the smaller numbers that we've seen from some of these other treatments in the rare and orphan indications. And that is to say, again, we have, pun intended, eyes wide open, about what it is that we're going to need to do to compete there in terms of the value proposition and the relative pricing strategies that we'll bring forward. I think our clinical program end-to-end, from the very first patients we dosed several years ago in our first-in-human intervention, through the dose response and follow-up, as well as the program that Steve and the team are installing really support all of that, there's not one thing, it's going to be a totality of evidence. And I would emphasize again, in such a large market, we know that safety is paramount as well. And I would say that was one of those things where you can be certain of, through the lens of programs that existed 5 or 6 years ago, when we developed the target product profiles, but certainly, we've seen further evidence of that emerge in the development of all the new treatments that have come forward, both clinically and those that haven't made it to the clinic.

Yes. Ken, just a follow-up to that, to you or to Steve, really. Is it worth it to do another wave of head-to-heads beyond Lucentis and EYLEA? I'm just trying to think -- you should be able to show noninferiority even to some of the next-gen agents, right, that have a little bit longer dosing interval because the efficacy is not that dissimilar, right? So you could tackle the next question, which is what about therapy X, Y or Z that may be coming down the pike in a couple of years.

Yes. I think that's 1 of the beauties and the derisking that exists within indications like wet AMD where, to your point, the actual functional outcomes that you see across these different agents is pretty similar. And the real benefit is that increased durability. So yes, after we've gone through our pivotal program, for our lead indication, there's always the opportunity in Phase IV to do additional head-to-head. But even in that time frame, I think there's really translatability to believe that the functional outcomes in a clinical trial setting even are going to be very similar, but the real issue is in the real world, what happens after a drug is approved and how close are patients to actually complying with whatever regimen that is, even if it is fortunately every 3 or 4 months, that still has to happen, to be able to replicate the clinical trial results that have been demonstrated. And to Ken's point about the totality of evidence, all of these things tie in to each other. So if you can have a onetime treatment that has that foundational anti-VEGF effect, that's what gives you comfort that you're not only decreasing resource utilization, but you're also ensuring compliance, basically, with a certain amount of anti-VEGF that can translate into better visual outcomes for patients and most importantly, preventing patients from going blind because they're not wanting to get their eyeball injected repeatedly for years.

That's helpful, guys.

And Ken, I just wanted to follow up on something that you mentioned about the potential pricing dynamic in a large indication such as wet AMD that does have available therapies. I mean, obviously, we've seen gene therapies today, like you alluded to, being quite expensive, which is probably driven by a combination of unmet need and maybe cost of production. So I guess when you look at wet AMD, is there sort of a target price that you would be going after? And I guess how does your bringing manufacturing in-house sort of drive your capabilities to offer 314 at a competitive price level?

Yes, sort of 2 independent variables there, Alec. But obviously, they ultimately can be related. And I would say that, again, I alluded to with Geoff, we built a model for assessing value of RGX-314 even before we dose a single patient. And I think that we implemented, even in our first-in-human program, long-term follow-up and extending into discussions with FDA and regulators, our pivotal program, things that we think are going to be important to emphasize the value of what the proposition of gene therapy for wet AMD is. And I think that, in that, we got to bring the data forward. I mean, look, we know what the prices of the drugs are that exist on the market. I would say that the payers, the insurers, the caregivers, the practices themselves, even to some extent, the patients -- I mean, this is a large market, right? So there's a lot of models, a lot of sophisticated thinking about what the existing paradigms are, what their real costs are, associated with managing those patients, and the derivatives of those things, right? Like I mean some of the biggest costs in these things are when the patients are lost, right? And then they end up losing vision again, not getting their treatments and then coming back into the system and starting from scratch, perhaps in a way that they can't reacquire what had been lost. Things like that need to be looked at and effectively can be looked at for the first time, right? Because often, our practices in our industry and even for the payers, it's not worth looking at something if you don't actually have a treatment to address it, right? You can characterize it and wish and hope that you have a solution, but we're bringing something forward now to the docs and the payers and patients that we think will deliver that. On the in-house manufacturing side, Alec, yes, I mean, we want to be as competitive and assertive with our involvement in gene therapy as we possibly can for years, since about the time that we went public, we hired a very expert team in biologics, manufacturing, process development, that has overseen the development of multiple processes that we brought into the clinic and scale and built a network and a real supply chain of contract manufacturing, blended with REGENX people and analytics and in-house capabilities. And we got to the point where we're ready to go to pivotal phase and starting to think about, okay, how are we going to deliver and supply RGX-314 to a market, we wanted more control over it. Frankly, it wasn't as much investing in a facility that was really going to drive, if you will, new efficiencies in the process. We could have done that in our process development labs and with a CMO. But I think having control, having end-to-end control over the bulk manufacturer, the fill and the supply of it to the market is incredibly important in validating and requires leadership that we've always envisioned that we would have with any product that we were developing. So we think we're going to be very efficient. We think we're going to be very competitive. We have with a lot of options in terms of where to go with respect to scale on a platform that we've used in patients already, and we have installed into multiple different GMP facilities and labs. And so now it's going to be a great opportunity to further expand that supply chain capability.

All right. Yes, it sounds like a good use of capital. I did want to sort of turn to the suprachoroidal a little bit and just sort of get us, from a strategic sense, I know you guys have been asked this in the past, how suprachoroidal and subretinal will sort of jive together if both ultimately are approved. I guess, do you have a sense of the regulatory process to add suprachoroidal later on? And would this be the preferred sort of method do you think going forward, if both are approved?

From a clinical standpoint, I think it's important to point out how far along we are with subretinal in terms of not only proof-of-concept clinically with safety and tolerability and delivering on our target of what we want to achieve, which is actually dramatically reducing treatment burden for patients. That basically is why we're very excited to be in pivotal development. Because we see with subretinal delivery, the opportunity to really fill this unmet need we've been talking about in the first half or so of this discussion. Having said that, it is a subretinal surgical procedure. So to the extent that you could have an office-based procedure, that really could expand the potential patients where the risk/benefit would be considered appropriate. And one of those examples is diabetic retinopathy, where we really see the opportunity here of advanced diabetic retinopathy patients who don't yet have diabetic macular edema or advanced proliferative disease the blinding complications of diabetic retinopathy. And there are massive numbers of these patients out there that are walking into their retina specialists every 3 to 6 months. And we know Lucentis works there. We know EYLEA works there. We know anti-VEGF works there. But as soon as you stop injecting into the eyeball in these patients, the severe forms of the disease come right back. So the unmet need there is even more substantial because there's these patients here that are more or less a ticking time bomb to develop these complications. But they're still asymptomatic and therefore, don't want to undergo repeated injections. So for us, there is the opportunity to potentially expand there. And that's why we're excited about suprachoroidal delivery, where we can deliver locally to the general area, the general target tissue for transduction, the retina. And I think our enthusiasm has really ramped up as we evaluated this preclinically and others like Peter Campochiaro at Johns Hopkins, had evaluated and showed the lack of inflammation with AAV8 in general and specifically with RGX-314, that really opened the door to this nonsurgical in-office onetime treatment option. Having said that, it's still much earlier days than where we're at with subretinal. So one of the beauties of subretinal is the immune privileged status of that subretinal space. So because of that, we don't have to worry about patients preexisting neutralizing antibody status to AAV8, for example, nor do we have to worry about immune-mediated inflammation requiring steroid regimens or any kind of immune regimens beyond what would be done for a routine vitrectomy. Those are things that we still have to learn about in terms of suprachoroidal delivery, where we're encouraged by our preclinical data and the data that we have to date in terms of safety and tolerability. And our first initial cohorts are step-wise looking at this where we started by looking at patients who do not have preexisting neutralizing antibodies to AAV8. And that's what we've looked at, for example, in the first couple of cohorts of the AAVIATE study in patients with wet AMD. And based on what we've seen to date, we've expanded that study to now start looking at even patients who do have positivity to preexisting neutralizing antibodies or NAVs to AAV8 in a third cohort that is currently enrolling, but we need to see these data read out in terms of dose response and safety and tolerability. So it's earlier days, and it's really going to take answers to some of these questions like whether neutralizing antibody status matters for suprachoroidal delivery et cetera, before we know how suprachoroidal would fit in relative to subretinal delivery.

Yes, Alec, I will add, because I think Steve's done a great job of summarizing, and I think the of thinking and the interplay between subretinal and suprachoroidal from a clinical and scientific perspective, when we step back, with the origination of RGX-314 as a pharmacological agent and how to deliver it, we always thought about building a long-term business here, right? You brought up earlier the fact that real leaders in this space and the business are continuing to innovate and advance even on top of their own existing infrastructure and capabilities, right, with the examples like faricimab and PDS standing on top of Lucentis and obviously, p of use, advancements with respect to Novartis having infrastructure to support Lucentis to first order. So that's what we want. We are looking at building an end-to-end business here around gene therapy. And at the regulatory level and at the commercial level, I look at the strength of standing on top of what subretinal is, to benefit suprachoroidal and the potential of suprachoroidal. Subretinal is very derisked right now for us, right? We're seeing great safety, great tolerability, really strong long-term outcomes in the clinic. And we've got the pivotal phase program with, alignment with the U.S. FDA including on things like our manufacturing process, right? That manufacturing process and that scale is going to be the same thing that we'll be using in our suprachoroidal approach, right? So that investment gets amortized over the potential of both of those scenarios. And commercially, as we start to advance ourselves into that pre-commercial planning and thinking, we start to think about the questions that Geoff was asking about how are we approaching the market on value and entering different spaces and justifying that value. Those exercises that we go through with suprachoroidal will be advanced by what we do in subretinal today. So I love the approach here overall. I think clinically and scientifically, our team has been all over it, but this has been part of the vision and the mission overall, not to just have a one-off product in wet AMD, but to actually build a sustainable business for decades. And I mean, as Steve alluded to, I mean, I think that a significant out-of-the-park type of swing for us is actually moving into diabetic retinopathy, without macular edema -- I mean that's just not something that we think we could afford to do from the sort of scientific or clinical risk-benefit perspective with subretinal. But we saw the pathway to go from subretinal wet AMD to suprachoroidal wet AMD, a potential for market expansion, but then a potential dramatic market commercial expansion through diabetic retinopathy. So I think we have a real sense that when we start to turn more cards on data in suprachoroidal, we're really well positioned.

Right. Obviously, diabetic retinopathy will be a large expansion opportunity, and very similar through of standard of care to wet AMD. So I guess, Ken, as a follow-up to that, and I do want to get to the rest of the pipeline and also manufacturing as well. But given Lucentis and EYLEA are also approved for diabetic retinopathy, do you see, sort of an accelerated path to approval, I guess, depending on how the non-inferiority studies pan out in wet AMD?

Yes. Then this ties in a little to the prior question, too, of how much streamlining can we do on suprachoroidal based on what we've learned from the subretinal. Certainly, in terms of learnings that we can translate or be efficient based on what we've learned in terms of dose ranging and advancing to pivotal. I think there is some learnings that we can take advantage of since we know what to expect with, not only sustained anti-VEGF, but specifically with RGX-314, if we're getting transduction in the target tissue from our subretinal program, but it is still a different round of administration. So I think there's only so much streamlining that we can do. One key aspect is we know, by precedent that after an initial indication with a given molecule, whichever that would be where you need the traditional 2 adequate well-controlled studies. When you seek to expand your label with additional indications like DR, traditionally, you only need one of those studies. So there certainly is that opportunity of expanding our label, so -- for either subretinal and/or suprachoroidal for that matter, where subsequent indications, you need just the 1 study. It's interesting, even though Lucentis and EYLEA have on their label treatment of diabetic retinopathy. Because of the hurdles that we talked about before of repeated injection in that specific patient population before they develop the blinding complications, clinicians and their patients are simply not signing up for this because you're basically signing up for repeated injections into your eye that you have to continue for the rest of your life unless you stop and then you have the disease come back. So we still have the opportunity, even with those labels that the reality is, the standard of care is still not proceeding, in most cases, to inject in these cases. So there's still the opportunity to do placebo or observation control studies and have very high power with reasonable assumptions to show an actual benefit, but importantly being able to do that with a onetime treatment that with suprachoroidal delivery is an in-office onetime treatment. And that's the package that our investigators and our advisers find so compelling about suprachoroidal delivery for DR.

Okay, perfect. Thanks, Steve. That's very helpful. And I think that was a great overview of 314. I did want to sort of change gears and talk a little bit more about manufacturing. Obviously, we alluded to it a little bit in terms of helping to better COGS longer term and also obviously having all that know-how in-house. But I did want to ask how your scalable suspension cell culture manufacturing. What are sort of the budding studies that need to be done there? And I guess looking longer term, do you think the 2,000-liter capacity will be sufficient to support your launches? Or do you think you're going to have to scale up as needed beyond that?

Yes, the relationship between some of the process and GMP batches that we were using early on in the history of our clinical studies and the suspension-based process, Alec, are very intertwined. And so therefore, from a scientific process and regulatory perspective, we've had very high degrees of comfort and sort of linear discussions that we're dealing with appropriate and proper engineering exercises that involve showing reproducibility and high levels of quality and output from the new system. But we're using literally the same types of cells, right? And what we did was we took the original master cell banks that we had, and we selected, basically kicked off colonies of those cells that, while they're naturally adherent, so they like to stick to the walls of things, we found things that would proliferate in scale in these bioreactors, right? And sort of allow us to take advantage of the types of things that bioreactors have afforded the biologics industry in general, in terms of scale and process control and any -- and especially downstream purification and so forth. And so when we took that to the FDA, for instance, at an end of Phase II discussion around RGX-314, there was a real expected understanding and again, quite a linear process from my view of how we were going to establish comparability of those 2 processes. And the reality was we've already been using the suspension process in other parts of our clinical pipeline in general. So we also had the comfort on things like quality, our quality system release criteria and those things that basically, we benefit from in terms of economy of scale across the entirety of that process. And yes, I mean I think, not trying to box myself in here, but 2,000 liters is a good scale to be at. I think as we look at the demands of the size of populations we're focused on, the doses per patient that we're looking at. And we have a pretty varied pipeline, right? We have probably the largest population that anyone's focused on in wet AMD and DR. But the intraocular indications tend to be smaller doses per patient per eye than what you see in other areas. And for us moving into areas like Duchenne muscular dystrophy and looking at additional programs like hereditary angioedema at sort of the systemic delivery level, they really are pushing the boundaries of, I think, where you need to take scale for AAV with the types of processes we have. So look, we've installed things at 200, 500 and 2,000 liters. So we have that flexibility, and the criteria and the assessment of our overall quality, the methods we use to characterize that quality and the potency of those products is all reproducible across those things. So now it's really just fun and exciting for the team to bring in a little bit more under 1 roof.

And Ken, that's actually a great segue into my next question, which was going to be on 202. And you guys have said in the past, I believe, that you think that 202 could be a best-in-class gene therapy for what is a pretty competitive development landscape in DMD. So I'd be interested to hear your thoughts sort of on where 202 fits in and some of the problems that are being solved with 202, other issues with other therapies.

I think that we view that our scientific approach and our drug development approach with RGX-202 for Duchenne has maybe 2 or 3 important fundamental advantages, Alec. One is in the scientific design of the actual construct itself and the treatment. And there's really 2 aspects to that. There's the fact that we've added something to the treatment in terms of the molecular biology of the design of this truncated form for dystrophin that doesn't exist in any other treatments that have entered the clinic yet. And in that case, there's 2 advantages to adding that. We've seen preclinically, and we look to explore clinically. One is that, it stabilizes the tensile strength, if you will, of this truncated form of dystrophin in ways that without having it, it does not. And the other is that, that function that we're putting back actually is involved in the recruitment of things, additional things that don't exist when you don't have that domain of the full-length dystrophin protein. So we view that scientifically, we're getting 2 big fundamental potential advantages here. One is, a stronger fundamental protein and 1 that recruits other things into this complex that stabilizes cells around dystrophin in general. And then the other piece is, we view that we're going to be entering the clinic with a commercial-ready process, right? So we're not looking to have to run additional studies on a go-forward basis. We're trying to start with something that we think can end-to-end clinical development all the way through commercial be supported.

Okay. Very helpful. And I wanted to turn to partnerships. Obviously, outlets using the NAV technology has brought in nondilutive capital in the past, and you obviously, major recent deal for Zolgensma. So I guess 1 question we've received is whether -- or I guess, which of the other NAV partnered programs could be next for approval? And I guess, what kind of economics could you then expect?

Sure. I mean it's a large set of things that are under license with our NAV Technology. In the last 6 months, I think we've seen the emergence of plans on the part of several companies to move into later stages of development. I think of Ultragenyx and their programs for OTC deficiency, in urea cycle disorder and another metabolic disorder, GSDIa. I think of partnerships we have with world leaders in the business of hemophilia, including groups like Takeda and Bayer who continue to bring forward what we think is a real, again, business-based approach to how gene therapy is going to play a role in what is already a well-served but important market for hemophilia with prophylactic treatments. We have partners like Rocket Pharmaceuticals who have reported early stage, but we think compelling data in areas of gene therapy in disease that may find wind behind their sales in terms of a rapid acceleration of the drug development and regulatory approval process. So overall, we've seen a lot of important validation that we think is meaningful. Several of, I think, our partners have also gone through integrations into larger infrastructures, like most recently a company we helped form, Prevail Therapeutics, was acquired, of course, by Eli Lilly, and they had started to report data and now we view that, of course, with the infrastructure and the capabilities at a place like Eli Lilly, the opportunity for additional advancement and acceleration through milestones is possible there. Of course, you mentioned the capabilities around AveXis, Zolgensma and now that's obviously a part of the product that's marketed by Novartis. So it's a true portfolio, Alec, I mean this is something that we established years ago in one of the, I would say, middle chapters of the history of REGENXBIO and how we were looking to learn about the technology, validate it, work on it ourselves organically but also work on its development through collaboration and partnership. And I think that it really -- of course, I think with the example of Zolgensma, with a lot of the other clinical milestones that have been achieved with NAV Technology, it really has been a part of sort of the leadership that we aspired in the field for this technology to deliver. And I mean, our own team, though, is focused on our internal pipeline when I think about capital allocation and even how to derivatize assets and capabilities that I'm excited about for the growth of REGENXBIO today, it really is about our internal pipeline, our capabilities and the engine that we're developing to be a leader in the development of our own treatments.

Perfect. That's very helpful. And I guess maybe in the minute or so that we have left, I think it's always nice towards the end to sort of wrap things up with upcoming catalysts that we could expect. Obviously, we've got the suprachoroidal data in 3Q, but I guess, for 314 or any of the other programs, are there any data updates that we should be looking forward to, over let's say, the next 6 to 12 months?

Yes. I mean, Steve and Olivier are very busy. We have certainly -- probably there will be multiple sets of data that come out from the suprachoroidal studies in the second half of the year with respect to wet AMD. We have guided to the fact that the Cohort 1 dose level will be the 1 that would sort of be the first trigger for an interim data update. But we have additional dose levels after that, and we have the diabetic retinopathy program as well. We've had a steady stream of data updates from our CNS neurodegenerative programs, our Hunter program from the end of last year to the middle of the first half of this year, and I think even more data in the second half of this year to sort of show the advancement of that program clinically. And next steps there for us are about establishing what our plan is overall for late-stage development. DMD, we'll have more data probably coming out preclinically at the time of the IND. It's going to be a major milestone for us to get that filed and then getting that second pivotal program launched and describing it a bit more in the second half of this year is -- that's a pretty robust story.

All right. Great. Well, I think with that, unfortunately, we're out of time, but I want to thank you guys for participating in the conference. And hopefully, we'll see you and everyone else in Napa in person next year.

Yes, Geoff, Alec, thank you, and thanks, everyone at Bank of America for hosting us.

Thank you, guys.

Thanks, Alec.