Good morning, everyone. Welcome to our Piper Sandler Healthcare Conference. My name is Yas Rahimi. I'm a Senior Biotech Analyst here at Piper. Excited to have the team from REGENXBIO here. Thank you for being part of our conference. We have a lot to cover over the next 25 minutes, but a wonderful place to start off is to get your thoughts on your vision that you have in 2025. What are some of the key objectives in terms of execution that are critically important for you? Great. Thanks. And thanks for having us. Much appreciated. Yeah, I think next year, this year has been super exciting, really kind of teeing up multiple programs for late-stage development. So when we think about next year, I just did an all-company meeting yesterday, and we've been together, many of us, for eight or nine years. And I said, "Next year is when we think we will have our first commercial product." And I think that's a huge advance for us, a big step forward. So the Hunter program, we're in the process now of filing a BLA. And then on top of that, we're building that capability, filing a BLA-licensed facility for some much larger opportunities in Duchenne, where we just started a pivotal study, which we would expect to enroll next year. We've got our subretinal studies, which are probably the largest gene therapy studies in the industry going, and those should complete enrollment next year. And then we're excited to start a new study in pivotal for diabetic retinopathy with AbbVie next year. So three programs in pivotal and one hopefully approval next year. Wonderful. Maybe I think investors recognize that REGENXBIO has been a leader in gene therapy, and it also has capabilities that maybe others are aspiring to have, which is your extensive internal manufacturing capabilities, which you see as a big strategic asset, so could you talk to walk us through what those capabilities are and how REGENX has improved upon them and why this is going to be an important asset for expansion? Yeah, for sure. I think over the years, gene therapy manufacturing, even if you listen to Peter Marks speak from FDA, it's the manufacturing process needed to mature, needed to evolve to where it was more commercially viable. And I think we've really accomplished that in the last few years. So about four years ago, we decided to internalize manufacturing. We were virtual at the time. And now we've got a state-of-the-art manufacturing capability, not just the bulk manufacture, but also the fill-finish capability internally. And I think that's just a huge asset when you think about programs like Duchenne, where very high levels of vector are required, having control over our capacity and having a really modern bioreactor-based process in place. Starting out early in the studies, not having to do a big comparability change is really a key asset for us. It's not cheap, though. Mitch will tell you about that, but it's well invested. Yeah. Thank you. Nothing that you want to do right is cheap. Would love to spend time on being a commercial company and the work that's being done at REGENXBIO to get ready for RGX-121 in Hunter syndrome. So let's start off from a, I think, on a BLA submission as expected, started in 3 Q. It's going to come to the finish line in 1 Q. What is the rate-limiting step? What has been completed? What is left to do in terms of bringing it to the finish line? Yeah, so this year we will have submitted by the end of the year the first two modules. One was non-clinical, and then the next one is the clinical module, and the last one to go in will be the CMC module in Q1. And that sets us up for a six-month review and potential PDUFA date in late Q3 or late Q4. The prep work that has been involved really is some of the big events that will occur next year. Acceptance of the BLA certainly is a key milestone, and then we'll have a facility inspection mid-next year that would move the facility to a commercial status, and then, again, our supply chain is under development now for the commercial administration of the drug. Okay. Since we just talked about manufacturing capabilities, what is the capability in terms of number of doses of RGX-121 that REGENXBIO could get ready by, I guess, end of year, assuming the PDUFA date? Yeah. So we have two separate production trains. We can run at least 50 batches on each side of that production train. So if you think about an ultra-rare indication like Hunter, I would expect that program itself would only consume maybe 5% or 10% of our capacity. Okay. Wow. Would love to, I think you guys have communicated that you see Hunter syndrome as sort of a $1 billion market in the next five years. You've also estimated that there are about 500 patients in the U.S., about 900 in Europe, and then about 165 in Japan. Could you walk us through where you got these numbers from and how accurate are they? And is that the possible TAM, or is that the TAM that RGX-121 could potentially penetrate the majority of these patients? Just kind of walk us through the market sizing. Sure. And then I can have Mitch help a little bit on just the overall market opportunity. The MPS community is extremely tight in terms of diagnosis and in terms of registries that have been created. There's about 500 patients now in the existing prevalent population, as you said, and roughly 50. I think that will increase in terms of incident population because of newborn screening. But we have several ways to find patients through diagnosis, through them actually registering on websites that we have for information about therapies. I feel like it's a group that we can easily access, and that kind of results in what would be a really compact commercial organization to address that. Okay, and is newborn screening going to be implemented across all states here in the United States, or is it going to be right now partial? It's partial now. We expect that to grow over time. And one of the things that drives newborn screening is availability of therapies, right? So it's sort of chicken and egg. But with our program and with Denali's program, we expect that that will be more prevalent over time. And for us, I think when we think about Hunter, early intervention is what we hear from the prescribers that have been working with us for years. And we've dosed patients as young as a year old to prevent the onset of disease. So tying in beautifully with newborn screening and our safety databases is comprised of some very young patients as well. That's very helpful. Maybe if you could talk about how do you foresee in this population, I guess, what the, not the eligible population, but who will be the first set of patients that you would want to get on therapy first? How do you envision the patient profile to look like based on the data that you have? Some of that will come out of the label discussions we'll have with FDA as to whether or not we're obviously pursuing a broad label. We've treated patients that have severe disease progressions, and also those that are at attenuated, so a lower level of disease progression. But again, I think along the lines of we would like to be in a position to treat really quickly after diagnosis and, again, more on the preventative side than what we'll find in the prevalent population where people may have advanced disease. But I think the key thing is, even if you're in that prevalent population and have advanced disease, the functionalities that we're helping them retain are absolutely critical. Being able to use an iPad, being able to speak, being able to hear are all precious things that patients at any age would want to prevent further degradation. Initially, you'll see, I think, that, and then it'll move more towards a younger point of diagnosis treatment. Okay. And how do you so between in 2025, after BLA filing and as we wait for the approval, what would be the cadence of bringing in the sales team, getting commercially ready? So I guess question number one is, what's the size of the sales force needed, and what's sort of the ramp of hiring that's going to occur? Yeah. I would say you don't actually need a huge ramp because it is an ultra-rare indication. And if anything, you probably need some more MSLs more than anything else. But I think the uniqueness of this opportunity is that many of these patients reside at centers of excellence, which we have great relationships with already. So in terms of a commercial lift, this is probably the best way to dip your toes into a commercial landscape. If anything, it actually gives us the nice foundation for our Duchenne program later on. Okay. And how do you, in terms of getting to the market, do you end up getting ready by launch, let's say, you get approved, you're ready to go, you go to centers of excellence and getting patients onto the therapy? How much awareness beyond centers of excellence, I guess what percentage of total patients are in centers of excellence, and how much work needs to be done to go beyond that size and build out? Yeah. I think you'll see us, as we get into the new year, starting to begin sort of preparing the market. MSLs will be one of the main methods for doing so. And definitely quite a bit of outreach on our side. We're actually going through the process now of qualifying sites that would be potential sites for commercial as well. So as Mitch mentioned, it's not a huge lift. And I think, again, because it's a one-time treatment, the patients may need to be near these centers of excellence, but once they're treated and the appropriate follow-up is conducted, then they don't have to do that. So it's a huge advantage of gene therapy. Could you maybe talk about post-approval and launch, how the capabilities for manufacturing and commercial readiness and Hunter Syndrome could actually end up translating into the other programs that are ongoing? What way will it open up doors for expansion and the cost savings associated by the first launch? Yeah. I think when we think about all the activities that are in preparation for a commercial inspection, all of those will have been done ahead of, let's say, a program like Duchenne or one of our retina programs. And I think that's just something that you can't replace. Although we do have a number of staff that have been involved with commercial programs, it's a new facility. You want to do that. So we're doing a lot of work as we speak today on pre-inspection readiness and quality systems checks as well. And because we have partners, we've actually been through a number of audits already internally. So we don't expect. We're hoping it's not eventful in that case. But also, having an experienced manufacturing team, you can envision for a program like Duchenne a quick ramp-up as we approach commercialization. Having an experienced crew in manufacturing ready to go is absolutely critical. Great. Let's maybe now transition into RGX-202 and DMD. I think pivotal data as expected in early 2026. I guess investors may need your help to understand how 202 could fit into the current gene therapy landscape. Could you maybe tell us, based on the product profile, what is the differentiation that it offers? Yeah. I think the real fundamental difference between our program and others is the inclusion of the C-terminus. And that goes all the way back to some papers that were published quite early on Duchenne, where compounds that were studied with microdystrophin, compounds that were studied with and without C-terminus, behave quite differently in the ability of the microdystrophin to assist in muscle repair. And so in the last year, we've actually repeated some of that work with similar constructs to ours and seen pretty significant differences in when a muscle is flexed, which microdystrophin allows for the force to be generated, that muscle gets damaged, and the C-terminus is heavily involved in the repair mechanism for the muscle. So it sets up more of a continuous loop, if you will, for exertion of the muscle. And ultimately, what does that mean? That should mean that over time, the effect of the product is more durable. We definitely see with that higher levels of microdystrophin in the older patients that we've treated. And that now is showing up as more pronounced functional benefit in at least the early patients that we've monitored. Okay. And I think some investors may be concerned since the Pfizer failure that it could have read-through to 202. Could we spend some time to understand why one should not be concerned and how these two products differ from one another and maybe also the clinical studies? We're certainly concerned about it in terms of learning from it and applying those learnings forward. And we haven't seen the depth of data that others might have regarding Pfizer in terms of what happened. Ultimately, the biggest difference is that it's not the same product. Different serotype, different promoter, and a very different construct in general. And so while we have high microdystrophin levels and we know Pfizer also had high microdystrophin levels in patients that they monitored, we have a definite difference in the way the product works and the design of the product. One of the things we already see different in the data set that we have in hand is safety. So we've got so far none of the adverse events that you've seen on myocarditis or liver damage that has been seen. One of the reasons beyond just the construct is potentially the immune suppression program that we've applied has, we think, a strong impact on less eventful dosing and better longer-term outcomes in terms of safety to date. We're really excited about that, and we think that's a differentiator as well. And with data in 2026, how soon could you file? And I think there's that notion that you might be far behind, but I think if you could just kind of close the gap on timing, help us understand that. Yeah. So I think we feel really optimistic about a filing in 2026, and we feel that that would be a result of full enrollment this year. The pivotal design that FDA reviewed and that we've implemented and now dosed our first patient in is for 30 patients. And we've dosed just this year with only a couple of sites in play, about half of that. So we're going to go as fast as we can go next year in terms of enrollment. And I think that will set us up well for top-line data as soon as possible and a BLA filing in 2026. And to your earlier question, that's why the Hunter program is so helpful because writing a BLA for the first time in any company is a big lift. We're doing that right now. So when we apply what we're doing now to the Duchenne program, all the modules, all the templates will be ready to go, and we'll be in a good position to go as fast as we can because we want to be in a position to address what we know will be a prevalent population that's available to us as soon as we can. When we look into the DMD market, there are about 15,000 total U.S. patients, about 25,000 in Europe and 3,500 in Japan. It's projected to be over $7 billion market opportunity. What percentage of the market and which patient profile could 202 address in that market given the competition? Yeah. I would also say right now, the current approved therapy is not addressing the market needs right now. So even though there's a perception that we're behind, the reality is we're not. I think if you actually look at the profile that we're looking at, we're basically going for age groups one and above. We're actually going for the entire market there as much as we can there in the ambulatory space. So we're going to have to see the data in terms of how we're going to what the penetrations are. But if you actually look at some of the commentaries our competition has made, the prevalent population would be addressed by 2030. As Curran kind of mentioned, we'll be on the market well before then. So time will tell as to what percentage of the market we'll get. But overall, we do anticipate not a fast follower, but we do intend to be the best in class once we're on the marketplace. Okay. Perfect. Well, we only have six minutes, but we have more to cover. Let's move on to 314 and wet AMD with regulatory submission expected on 1H 2026. So there are two wet AMD programs with AbbVie, right? One is the subretinal wet AMD and two global phase III studies, and then this suprachoroidal wet AMD, which is in phase II. So maybe let's start with the subretinal. I guess some investors might be thinking about inflammation due to a competitor retinal gene therapy program. So could you talk about why you don't foresee inflammation that could be an issue in the subretinal delivery? Yeah. I think to date, our experience with the subretinal administration has been incredibly positive around safety. You're getting to an immune-privileged section of the eye. One example of that is recently we published data on fellow eye treatment. So patients that had been originally treated with 314 subretinally now getting their fellow eye treated. That wouldn't be possible if you were developing immune reaction to the therapy. And I think that's one of the big advantages. And so on one hand, you have an OR-based procedure, which I think will take time for us to address and develop to make that easy for a commercial indication. But on the other side, you have five-year durability being demonstrated, really, really good safety, and most importantly, sustained vision for patients that were treated. Okay. And then team, what do you see on a blinded safety front from both of your ongoing ATMOSPHERE and the ASCENT studies that you publicly can speak about? Yeah. We certainly can't comment on the studies as they are blinded, but we do have regular internal safety monitoring and external safety monitoring that's conducted. So if there was anything going on regarding safety that required a change or such, we would know about it. Okay. And big picture, how do you think your gene therapy product differentiates in this market? I think the one-time promise of a gene therapy, where I literally was talking to one of our surgeon trainers who had been part of an OR procedure. That patient's out seven years now, never had to go in for a supplemental injection. So that's the promise I think that we're looking to fulfill, is that I describe it some days. One of the main missions of the company is for people that hate to go to the doctor. Nobody wants to go in every month or even every six weeks to get an intravitreal injection if they can help it. And this is really the fundamental of why we're here with the gene therapy approach. Yeah. And I would also add the real-world evidence has supported that notion because many patients, actually, unlike the clinical studies, have actually stopped going back for a follow-up. So that is supported in the real world. Wonderful. Let's, in the three minutes now, transition to another exciting program of a very high unmet need, which is 314 diabetic retinopathy. And you're going to start a pivotal trial in the first half of 2025. So how do you think about the registrational program for diabetic retinopathy? It's a fairly straightforward plan. There's regulatory precedent for DR in terms of either two-step worsening or two-step improvement being an accepted primary endpoint. And so I think actually because there are products already approved for diabetic retinopathy that don't have very high adoption because they require, as we talked earlier, monthly injections in patients that really won't tolerate that, it's a perfect fit for gene therapy. How do you, in terms of enrollment of patients, have you thought about who would be the ideal population to enroll? Are there subpopulations to exclude to ensure further clinical success? I think the main emphasis for DR, as we think about gene therapy, is early intervention because you want to prevent worsening, and so we're looking for patients that have less advanced disease typically so that we can prevent the ongoing worsening of the symptoms, and that's what allows us to go into the suprachoroidal administration with a lower dose is that disease activity is lower initially, and that also helps us with a better safety profile at that point, so again, I think we will always be looking for early intervention with this therapy. Okay. Definitely, REGENX is going to be very busy embarking on being a commercial company beyond the successful clinical execution. What is the current cash and cash runway for the company to fund all these programs? Good question. Our current cash runway will get us into the 2026 timeframe with pending milestone payments from our collaboration with AbbVie, potential monetization from our PRV on the 121 program. That will get us deep into 2026, if not even 2027. Excellent. Let's thank the team for a great discussion. We're very much excited going into 2025, so very first approval.