Good afternoon, everyone. Hope you're all doing well. My name is Cabrel Happi, and I'm here with TD Cowen. Thank you so much for joining us today. We have a presentation that's going to be led by CEO of REGENXBIO, Curran Simpson. Without further ado, I'd like to welcome him over. Thank you again for your time.
Thank you for the nice intro, and thank you for the invite. Thanks for coming over right after lunch. Much appreciated. Really thrilled to talk to you a little bit about REGENXBIO. I will be making forward-looking statements. There will be a quiz after this as to what was on line 12 for those that want to take a quick peek. Let me just talk a little bit about the company. We are one of the founding gene therapy companies that have been going for 15 years. We originally started out as a licensing organization. Zolgensma, which is a huge product for Novartis, came from our original IP. Over time, we decided we'd rather internalize development, develop our new products internally, and do less licensing. That's how we've pursued the last five to seven years.
Our vision is a world where debilitating diseases can be treated with a one-time therapy. Our mission is to seek how to improve lives through the curative potential of gene therapy. The areas that we're pursuing are significant. Our lead program in terms of near-term commercialization is RGX-121, which is for Hunter syndrome, represents a market opportunity up to $1 billion. We have a Duchenne program that I'll talk about that represents a market opportunity of potentially $7 billion. The wet AMD programs, which are partnered with AbbVie, is a huge market, $18 billion, and growing every year. Large, significant opportunities within our portfolio. As I look at our pipeline, I'd like to mention, as I mentioned, the RGX-121 program, we're in the process now of imminently filing our last module of the BLA for that program. Our first BLA as a company.
Yesterday, we were pleased to announce the closure of the deal with NS Pharma, which got through Hart-Scott-Rodino review. That is a significant partnership for us as we move towards commercialization. I will talk a little bit about that partnership later, but we are thrilled to announce that closing of the deal. We have a major program in Duchenne, which just last fall entered a pivotal stage. We have released really interesting data over the course of last year in terms of safety, biomarker data, and then later in the year, functional data. We are really excited to be recruiting patients now in a pivotal phase. We have this large retinal franchise that is partnered with AbbVie. Two modes of administration are being explored. One is subretinal, which is an OR-based procedure for wet AMD.
We're getting close to closing enrollment on two large studies, almost 1,200 patients across the two. We're looking forward with AbbVie this year to moving into a new mode of administration, supracoroidal, which is an in-office procedure for diabetic retinopathy, with phase I and II studies still going on for supracoroidal administration in wet AMD and DME as well. For a 345-person gene therapy company, we've got a lot of really valuable late-stage assets that we're excited to continue to develop. What's in store for 2025 and 2026? These are really, really important years for us. That's why we titled it. I think we stole that from somebody, but the future is now. I've been with the company for over 10 years. Every year, we talked about getting closer to commercialization. Here we are. We're getting very close.
As I mentioned, imminent filing of the last module of our BLA for RGX-121, which is being filed as part of an accelerated approval potential for Hunter syndrome. As I mentioned, now partnered with NS Pharma. We also this year will report additional phase I and II functional data for our Duchenne program. We gave an update last November and will further that update during this year. We also intend to complete enrollment of our pivotal study for the program this year. We started that late November off FDA feedback and are doing really well with enrollment. Excited about the potential there. As we've disclosed earlier in the year, we intend to complete two large pivotal studies for subretinal with AbbVie. One's called ATMOSPHERE, and the other one's called ASCENT.
ASCENT is interesting in that over time, we've globalized the program with AbbVie and their recruiting in Europe as well. Real excited about the potential there. For diabetic retinopathy, we're planning a pivotal program to dose the first patient in this year. In 2026, even more exciting, commercial launch, we hope, of 121, pending a successful review and approval. Top-line pivotal data from our Duchenne program, top-line pivotal data for our subretinal program. A lot of catalysts and milestones over the next two years for very large opportunities. One thing that differentiates REGENXBIO from others is that we have our own in-house manufacturing.
That was a decision we took a couple of years ago, realizing that all the way from Peter Marks criticizing gene therapy manufacturing as immature and needing development, we've invested over the last seven years on what we feel is really a top-line commercial-ready manufacturing process that particularly can support the Duchenne program, which is a high-dose indication. We have control of our own internal manufacturing, including fill-finish capability. It is a really significant differentiator for us as we think about commercialization. I'll talk briefly about RGX-121. This would be the first gene therapy potentially approved for Hunter syndrome. There are no effective cures or treatments available at this point. The unmet need is significant. RGX-121 has the potential to treat up to 70% of MPS2 patients.
We've already shown our pivotal data about a year ago, which was successful in reducing a biomarker called D2S6 close to normalized levels. We feel we presented that data to FDA in our pre-BLA meeting and got very positive feedback. We feel very positive about our eligibility for accelerated approval. As we mentioned, our partnership with NS Pharma also helps us on cash runway. There's a $110 million upfront payment that was made or will be made as part of the deal closing. Even more importantly, partnering with NS Pharma allows us to bring this product to patients faster. They have an existing commercial infrastructure, and we will manage this commercial supply chain for the program. Really exciting developments here. The prevalent population for MPS2 is significant. There's almost 500 patients in the U.S. that have MPS2.
The incident population is roughly 50 patients per year. A significant opportunity that we look forward to developing with NS Pharma in terms of commercial outlook. NS Pharma, as you know, has deep experience in rare disease commercialization. As well, the deal structure allows us to receive up to $700 million in sales milestones as part of the launch and sales performance. Really not just adding short-term benefit to REGENXBIO in terms of our cash position and ability to commercialize, but long-term value being recognized as the program progresses. This is something that we're launching actively now. Given that we're roughly nine months from launch, you can imagine the planning and activities that are occurring on the commercial side, which is where we wanted to be. I won't go into too much detail here, but this is our first BLA as a company.
That's always a significant element. I think there's two elements of it. One is obviously we're excited to submit the final module of the BLA for Hunter. We're really proud of the data that's been generated. The patient community is anxiously awaiting new therapies. More importantly, from a strategic standpoint, this sets the stage for our Duchenne program as well. Writing your first BLA, you develop all the templates, all the ways of doing it. You have the review process in hand. We basically are looking forward to repeating that entire process next year as we prepare our BLA for RGX-202. Speaking of which, RGX-202 is on track to be the next gene therapy for DMD. We think we have the potential to be second to market.
That's significant because when we started this program two and a half years ago, we thought we might be fourth to market. We have made up a lot of time, and we have had really important results over the last year, starting first with safety. I will cover in detail the safety and efficacy data that we have to date, but also extremely encouraging interim data, especially in older patients where we are seeing high levels of microdystrophin expressed in those patients. What differentiates us coming second to market from the approved product is the inclusion of what is called the C-terminus in the construct, which we feel, and actually, if you go all the way back to the adcom for Elevidys, was mentioned, that it makes our microdystrophin more like full-length natural dystrophin and has an important element in repairing muscle once the muscle has exerted force.
We feel like not only are we potentially second to market in a large indication, but providing potential for additional functional outcomes that would be positive based on the differentiated design. This is a program that is top of mind for us. Our main goal this year is to enroll the study as quickly as we possibly can and beat the timelines that we've set out publicly. I think the market for Duchenne is being defined as we speak. We see really good uptake commercially. Zolgensma led the way for gene therapy, but I think people were looking for what's the next Zolgensma. I think Elevidys is following a similar path in terms of sales. I feel like there will be a significant amount of the market available, presuming a potential approval in 2027.
We feel that the prevalent market will still be quite wide open in terms of entries for new products. We can manufacture, again, back to our differentiator in manufacturing, 2,500 doses per year internally. That is a significant level. If you think about patients treated for Elevidys this year, estimates are something in the range of 1,000, maybe 2,000-3,000 next year on consensus estimates. We can make that in one year in our own manufacturing capability. We intend to begin commercial build next year to be ready for that. This is just a pictorial of constructs that are either approved or in the clinic. I wanted to point out the comparison for our program. You see RGX-202. At the end of that, you can see the C-terminal domain that differentiates it.
One of the reasons that some of the early constructs may not have had the CT domain included is the cassette size for AAV is limited. You can only package so much within AAV. There was a constraint that if you included the CT domain, you couldn't actually produce AAV vector to produce this transgene. We've worked out ways with our proprietary manufacturing process to do that and to produce a product, which interestingly is at 80% full capsid with a really high degree of genomic integrity. This is a technological advance we've made in manufacturing to enable this differentiated construct to be made. We're real excited to implement that. This is just a pictorial. I'll just have your eye train to the orange bar. The blue bar is microdystrophin devoid of the CT domain.
It's not identical to anyone else's in either marketed product or in the clinic, but it is a "standard microdystrophin." The orange bar is that same microdystrophin with the C-terminal domain included. This study measures a muscle flex 20 times to look at the initial force that the muscle can withstand. You can see a clear difference preclinically in the ability of the C-terminus to affect function and resilience of the muscle to repair itself. We think this is underpinning a clinical benefit that we're hoping to see as we start dosing patients and look at long-term outcomes that on a functional basis, those patients might have more opportunity to benefit. What have we accomplished in the last year that's gotten us to a pivotal study this year? So far, we have a really exceptional safety profile for this program.
No SAEs to date in 11 patients treated and no AEs of special interest, which is really significant. We have a proprietary immune suppression regimen that we employ that we think helps with this and definitely reduces the burden of monitoring for patients post-treatment as a result of it. We are really pleased with that. I will show some data on the next couple of slides. The biomarker data that we have produced to date also shows very high levels of microdystrophin. Particularly, many of the patients we treated early were eight and older. In those patients, other studies have shown fairly low levels of transduction and expression of microdystrophin. We are seeing much higher levels, which gives those children a better chance to benefit. We are seeing that in some of our early functional data, which is really exciting. I like this table to be as boring as possible.
As you can see, a lot of zeros in terms of these are AEs that have been noted in other studies. Common AEs that are found are elevation of liver enzymes and complement activation. We're just not seeing that in our study. I think that's highly encouraging. I think highly encouraging also from an enrollment standpoint. People thinking about whether or not they want to go on to a clinical study, this is the first step is to review safety. I think we're being sort of favorably reviewed at the investigator level when they see this. Also, as importantly, we did a dose escalation study last year.
We started with dose level one, knowing that we wanted to ultimately get to dose level two because our preclinical data showed that we could restore function in the MDX mouse model, roughly equivalent to wild type at the higher dose. We were always heading towards dose level two if we could show safety at dose level one and then dose escalate, which we did. At dose level one, you can see some of the different outcomes, but we saw microdystrophin levels in the four to seven-year-olds, around 60%, very high % positive fibers generated. Interestingly for our programs, very high vector copy number results, which indicates good biodistribution in the program. Why is that important? For two reasons. One, biodistribution is great, even better if it's localized where it needs to be on the fiber, which you can see from some of these slides.
Second, it could lead to longer durability of effect, and because of that, this is something that we're really hoping in our two-year data will be borne out and beyond. Now, you can look at the dose level two data, and you see obviously the vector copy number is going up, higher dose, double the dose. A lot of vector ends up in the liver at lower doses, and so it doesn't get necessarily to the muscle where you want it. As you go up in dose, more of it gets to the periphery where you do want it. You can see that in these numbers: 55 vector copy numbers per nucleus is really exceptional. As exceptional as that is, the microdystrophin data at 77% in the four-year-olds and then 40% in the 8-11-year-olds.
That's an N of five in the eight to eleven. It is getting to be a more significant data set as we proceed. Comparatively, other programs are showing much lower levels of microdystrophin in these older children. That is one of the differentiators we are seeing with the Duchenne program. This is data we put out in November for some of the timed function tests. This is ultimately what matters to patients and to the community: how are the children doing? How are they progressing? These are data against matched external controls. We have a database of roughly 400 patients that we pull from, and we match these patients to those natural history outcomes. You can see in the blue bars, this is the NSAA development at dose level one for those patients at 12 months.
You can see what would have happened if in the natural history setting they were not treated. These are really, really significant differences in function. I keep saying it, hopefully it comes true. If we can just reproduce this in our pivotal study with 30 patients, we have a great story for FDA. I really feel like we are on to something big here. Now, turning to dose level two, a little less data available at this point. These patients were treated in the latter part of last year. Just as impressive results, I will admit with an N of two patients, one of the patients is doing incredibly well. 10 NSAA improvement, I do not think has been reported in any other gene therapy study. We will need to widen that data set out with additional patients, but I will take it.
I'm sure the patient will take it. We have a video of that child riding a bicycle through Manhattan. They'd never been able to ride a bike before. It's pretty moving to see it. We really, really enjoy seeing this data. Where is FDA looking? NSAA, if you think about Duchenne, if you followed it, was sort of discounted as an indice because it didn't read out as positive in other studies. Our data looks fantastic on NSAA so far, but also time to rise or time to climb as well. Those are other indices that are important. We're measuring all of these. The full data set is ultimately what we're looking forward to reporting out through the course of this year as we get more data. Off to a great start. We also monitor caregiver-reported function as well.
These are things that the children were able to do post-treatment that some of them were not able to do before. There is the video of the child riding the bike and running, participating in recreation, and walking in the community. Things that are not sort of sterile clinical data, if you will, that are really, really important to the parents of these children. We have been pleased to be helping and improving lives in that way. Stay tuned. We are going as fast as we can. We have a lot of enthusiasm in the patient community for enrollment. We feel like enrolling the full study this year is well within our reach and that will enable us next year to report top-line data and file our BLA. Switching completely across to a different topic.
As I mentioned, we have a large program in our Retina franchise partnered with AbbVie. This is something that we've been working on since Jim Wilson's lab nine years ago in the ocular space. The subretinal studies were started initially independently by us. Sort of midway through those studies, we signed up the partnership with AbbVie, who has an awesome commercial infrastructure to help us maximize value. We have two routes of administration in the clinic, subretinal and supracoroidal, so getting to the outside of the eye and to the inside. Both are in studies. In the SR study I'll show is in late-stage pivotal studies. We'll complete enrollment this year, top-line data next year. Supracoroidal studies, we'll start a pivotal study in diabetic retinopathy this year. The wet AMD and DME studies are ongoing in phase one two still.
Huge unmet need in terms of retinal centers being overwhelmed. Gene therapy may provide an opportunity to take patients, particularly patients who are, as some of the docs call them, frequent flyers, who are needing 12 injections a year on average. We have data on the subretinal program, which I'll show, that takes us out to two to three years now of durability being shown, stable vision and minimal supplemental injections. It's really exciting. The wet AMD market is expected to grow substantially over the next 10 years. Probably up in the $30 billion range is what we're hearing and what people are estimating. We have, to be transparent, people say subretinal, it's an OR-based procedure. Who would use it? The feedback we get is that 10%-15% of the market would potentially use it, especially those with severe disease.
10%-15% of $30 billion is well worth pursuing in gene therapy. I'm real excited about the potential for both subretinal. Following behind it, supracoroidal, which is an in-office procedure, could unlock even further value. As I mentioned, these are large studies, ATMOSPHERE is roughly 540 patients and ASCENT at 660. Very large global studies. As I mentioned, we're recruiting in Europe now, ASCENT as well, because the intention for AbbVie is to file these BLAs, and they have responsibility for that globally. We are continuing for phase I/II studies in supracoroidal for DME and for wet AMD. Those are still in the dose ranging studies. Very interestingly, on diabetic retinopathy, I'll show a little bit of data with the time left. We see really interesting results on.
Lucentis was approved for diabetic retinopathy, but the use is very low because most patients who have diabetic retinopathy do not want to sign up for a monthly injection. Gene therapy is a perfect fit for that because the one-time administration is much more attractive. We are delivering the same transgene as we are in subretinal. This is just showing you for subretinal. Here are patients that are three or four years out with stable vision, minimal supplemental injections along the way. Long-term durability and, very importantly for gene therapy, ocular is very good safety profile. Very little intraocular inflammation is being shown. We are pointing towards top-line readout of this data next year. Subsequent to that, filing of the BLA.
For diabetic retinopathy, when we think about the only administration that would be feasible if the market is not willing to sign up for monthly injections, they're also not probably willing to sign up for subretinal administration. We developed this program from scratch using the supracoroidal administration. It's called the Clearside device that's been approved in other types of programs. It's a commercial device. I'll just show you some of the data here. On the left, you can see the control group over the course of, I think this is the 12-month data. Yes, one year. You can see a certain number of the patients worsening, some with no change, but very few improving. You can see the control arm of the study, I'm sorry, the treatment arm of the study showing no one worsening and either stable disease or improvement.
The concept in diabetic retinopathy is upon diagnosis, treat these patients early and minimize the progression of DR, which will eventually become, will worsen. We are really excited from this data to show that. There are two different regulatory endpoints available for that two-step worsening or two-step improvement that we are following. This is also showing vision threatening events, huge reduction, 37% in the control arm versus 4% in the treatment arm. Really nice improvement using the supracoroidal administration. To summarize, really excited about the potential with Retina, with Duchenne, near-term with Hunter. I do not know of another gene therapy company positioned with such a broad portfolio with these late-stage assets that is in the same situation that we are. We are really, really excited that, as I said earlier, the future is now for the company.
We are really excited that we are on the cusp of delivering these therapies to patients. I thank you for your time and appreciate you coming in and hearing our story.