Good morning, everyone. Welcome to day one of our Piper Sandler Healthcare Conference. My name is Yaz Rahimi. I'm a biotech analyst here at Piper Sandler. Really thrilled to have the team from REGENXBIO here. 2026 is a big year for REGENXBIO. You guys have been the pioneers in gene therapy. Would love to kind of start off the role that sort of your views into 2026 and how you're thinking about some of the key inflection points, and then we'll go through each program one by one.
Sure. Yeah, it's a really big year for us in terms of we have really solid dates in mind for some really key milestones. The first is first quarter, February, PDUFA date for our Hunter program. I've been with that program for nine years now, so it's exciting to see it getting to this point of review. We've had good success over the summer with the inspections. Next on the list is in early Q2, we've guided to top line data for our Duchenne program. We completed enrollment last October and look forward to the results there. I can talk about more in depth on that. In September this year, we announced completion of enrollment. I think they're the largest gene therapy trials ever conducted with AbbVie.
We are now pointing to top line data for the subretinal program for wet AMD late next year.
Wonderful.
Lots to look forward to.
Lots to look forward. Lots of rich catalysts that are here upcoming. You guys have made a tremendous amount of investment and work and hard work went into building a manufacturing facility. Help us understand sort of the capabilities that the facility has as one of the leaders in the gene therapy space.
Sure. Yeah. We started probably around 10 years ago when I joined building up the CMC approach. I think historically, FDA and others have been pretty critical of gene therapy manufacturing, saying it needed to be modernized. That is exactly what we set out to do. If you walk into our manufacturing facility located in Rockville, it will look like a biologics plant, suspension bioreactor with HEK293 cell line that we use. We have really sort of cracked the code on gene therapy expression levels for vector. We have published some of that at ASGCT. I think importantly, having control of manufacturing, particularly for the Duchenne program, which has a really high vector requirement, is a huge asset to us, a differentiator.
Wonderful. Maybe let's talk about RGX-121, which is upcoming here with PDUFA data in February. I think recently you noted that the inspections have been completed. PDUFA data is on track. Just kind of help us understand sort of what is left to do between now and PDUFA and what your disclosures are going to look like between now and then.
Yeah. We'll certainly give a disclosure around February when the PDUFA date comes. The BLA was submitted as a rolling BLA. We submitted non-clinical, then CMC, and then the clinical module last. As you could expect, most of the review at this point is down to the clinical module. We published data in September with full 12-month data on all of the patients in the pivotal, which looked really exciting. Yeah, we're looking forward to proceeding to a PDUFA date, hopefully a positive decision. I think the manufacturing plays into that as well. The facility was inspected as part of that in the summer, and we got out of that with no observations, which is pretty rare. We feel like we've de-risked one key aspect of the gene therapy world in terms of CMC and non-clinical, looking really positive.
It would be also great to think about sort of how you're envisioning commercialization and be transitioned to become a commercial company with manufacturing and scalability on hand, which will be what maybe a question that comes up is like finding patients, warehousing them, what work has been done, hires in terms of building the commercial team.
Yeah. We signed a deal early this year with NS Pharma. We are in a partnership in which NS Pharma will handle the commercialization aspect. We felt it's a bit too early for us to build out a sales team for an ultra-rare indication. The benefit we have is we do control the manufacturing supply chain. We'll have a lot of input, obviously, into the commercialization because many of the sites we're going to will be the same as what we used in the clinic as well. MPS is an ultra-rare disease, and finding patients is actually pretty straightforward. There's emerging, I think I heard 40% of the states in the next year and a half will be doing newborn screening. That will be an automatic funnel to find patients.
They're very aware of our program. have had a 10-year relationship with the MPS Society that will help us greatly with that. We are looking forward to it. I think we have all the elements for a successful launch.
How do you think 121 will play into the market?
I think one-time gene therapy is really, truly differentiating. If you think about the burden of care, which currently there aren't any treatments available for the CNS manifestation, for things like enzyme replacement therapy, patients have to come in many times weekly for infusions. Imagine the burden of having a child. A one-time gene therapy, I think, will be a very powerful alternative for patients. We expect really strong adoption.
Wonderful. As many investors are also aware, first of all, you will be the first gene therapy to enter the ERT market, which would be another key milestone for the space. Investors who follow the program understand that DNL310 also has an upcoming PDUFA date on April 26. Maybe help us understand sort of the evolving landscape when it comes to the space with multiple gene therapy programs available and the differentiations of them.
Sure. Yeah. I just talked to a couple of people within patient advocacy groups. It's been 20 years since they've had anything new approved. Having two programs potentially approved is great for patients. I like our position in the sense of a one-time gene therapy. I think our data, particularly we have data in younger patients. I think in terms of who are the right patients to dose and coming off newborn screening, once the damage is done, it can't be undone. Early treatment is going to be important. I think the strength of our data is in that younger patient population.
Great. Team, would love to talk about 202 and DMD. Maybe start off with helping us understand what is the strategic interest in 202 for DMD?
Yeah. I think it plays on a lot of strengths within the company. Number one, it's in rare disease, which we just talked about the Hunter program. That's a key element of our portfolio. Number two, our Chief Scientific Officer, Olivier Danos, has been working in Duchenne for 25 years or so. He had a lot of input, obviously, and drove the design of the construct, which includes the C-terminus. If you go all the way back to the 11S AdCom, you'll see FDA reviewers talking about the value of making microdystrophin more like natural dystrophin. That automatically includes, if you do that, the C-terminus, which we were able to accomplish. What that does is it helps with restoring function once the muscle has been damaged through exercise. That gave us promise of delivering better functional benefit.
I think the last piece of the puzzle, maybe there's two more, but one is the immune suppression regimen that we're using. So far, we've had no SAEs in our phase one two study. We'll be happy to roll out our safety update in Q2 top line data. We feel very positive about that. Then playing into that is the manufacturing process. We're at 80% full capsid. The majority of the product is the intended product. That's what allows us to maximize the dose and give the best possibility for functional benefit.
How do you think it differentiates versus other gene therapy programs in DMD?
I think that if we look at our phase one two data and we look at the benefit to risk profile, I think we have the best product in development. I say that because we're seeing improvement in patients that are seven and older, where automatically those patients are normally in a decline phase of their disease. We're seeing those children improving in function, not just stabilized. We're also, as I mentioned, not seeing safety events. Put the two together, I think we have a compelling case.
The data is on track for Q2 of next year. Maybe just housekeeping items. What type of data will you have on hand at the time of the disclosure? What is sort of the bar for success or the expectation going into the readout?
Yeah. We'll have in Q2, we'll have for all 30 patients, overall safety update. We'll also have data around the primary endpoint, which is microdystrophin, the proportion of patients at 10% and above for microdystrophin. We'll also have functional data, I would say on roughly a third of those patients. It depends on visits and timing, etc. Key is at 12 months. We don't believe data earlier than that because it could be subject to immune suppression, etc. More importantly, that's what allows us to match to the external controls because most of the NSAA data for external controls is a 12-month data point. What success looks like is we want to see differentiation on time to rise, but even more importantly, I think on NSAA, which we haven't seen in other programs.
That is what we are seeing in our early phase one two data at the pivotal dose. Same safety, same fun. If we can just replicate what we have done in phase I, II with 30 patients in the pivotal, we will be in great shape, I think, in terms of the application.
Team, obviously, the data readout is critically important, but what is your plan past that data? Obviously, you'll be getting ready to file. Is this something you want to embark on commercializing on your own, or are you actually actively looking to partner in this program? What are some of the key factors as you're going to be making that decision, obviously, post the data?
Yeah. No, I think we love having the program on our own within our full control. The program to date has been largely U.S.-based. Moving as fast as we can to an approval in the largest market. We're definitely open to a partnership that could broaden the scope of the program to a global enterprise, but I think that's not our current near-term focus. We have everything we need to do it. We've got the manufacturing capability. We've got a sales team that's being brought online as we speak. We'll be ready. We're pointing towards an initial BLA filing in mid-2026.
Perfect. Team, Curran, you alluded to sort of the commercial capability. The advantage of getting ready for 121 and then for the DMD program, sort of the learnings and the capability of scaling up. If you could just touch, even though these are different programs, different constructs, there is a lot of read-through when it comes to scalability of manufacturing.
Yeah. I think there's a couple of things. Number one, having a facility that's been inspected with no observations, that will be the same facility that's used for the 202 program. We feel that element is de-risked. The process looks almost identical, just a couple of changes there. Interestingly, as well, the partnership with NS Pharma will help us on the supply chain aspect, delivering to patients. Do not forget, we also were the initiator early on of Zolgensma. It's our IP. Many of the dosing sites for Duchenne are also the same for SMA. There's a synergy there that we're learning from as well.
That's great. Another big readout will be actually the 314 readout in Q4, the pivotal study, which is in Wet AMD. Maybe before we go there, just give us sort of a recap of where we stand currently in the current Wet AMD market. I think that the market is driven by anti-VEGF and TKI therapies. Maybe help us understand the rationale for subretinal delivery and the importance of it and what would that mean in the market.
Yeah. I think certainly Wet AMD, I think the last estimates I saw were between $6 billion and $8 billion, and it's growing. By the time we would launch, it could be above $10 billion. Probably the largest market that a gene therapy is being developed in. We went with subretinal because that's really a validated method of applying a gene therapy. It's also very free of safety events. As a first entry into gene therapy, we decided to start with subretinal. Even though people think it's awkward because it's surgery, there's actually tons of vitrectomies done every year. Retinal surgeons want to do surgeries. We think there's a meaningful space for subretinal gene therapy. We did a study in the course of developing 314. We call it the bioreactor study. It was basically a crossover to the commercial process.
If you just look at that data and that replicates in our pivotal data, which we think it will, we're going to have a really exciting product.
Are your partner at the what are some of the financial obligations for at the end of a successful study that's going to be reading out?
I got to get Mitch in the game.
Yeah. Yeah.
Once approved, there are some regulatory milestones associated with it. When it comes to profit sharing, it's 50/50 in the U.S. XUS will be a sales royalty. We have not disclosed the exact figures there, but it is a pretty lucrative market. Just to add on a little bit more, the procedure itself is not very tedious. Many of these doctors, it takes about 20-25 minutes at most.
Oh, wow.
It's actually not as cumbersome as some may believe.
Wow. What is your partner and what do you guys are thinking? I think you alluded to the market is right now $8 billion. It could grow to $10 billion. You're assuming this could be a $2 billion product. What is the size of the population that could be eligible that you would think would opt out?
I think at any given time, there's roughly 100,000 patients with Wet AMD. That is also growing over time. These retina centers are overrun. They don't want to take on a lot more patients. Gene therapy is a great solution for that. One administration. We've got patients out almost four years now with no additional treatment required. I think AbbVie sees it as a huge, they will carry the commercialization of the product. We'll certainly have input given the development history we have. Think about their sales force and muscle. They've got 7,000 MSLs. There's a lot there. They're investing deeply into this program over the years. I think now that we have a solid top line data late next year, I think you're going to start to see them getting more involved with commercialization activities.
For investors who are revisiting REGENXBIO and looking for the catalyst, what was the study power to show? What do they need to achieve?
Both studies are non-inferiority studies. One is against Lucentis, and the other is against Eylea. There are also two active doses in each study. They are highly powered, 600 patients each study. We feel like our probability of success is positive here.
Great. Let's maybe take a few more minutes to talk about RGX-314, which is in diabetic retinopathy, a very high unmet need. Maybe you guys are very active in kicking off the study. Maybe help us understand sort of where are you in the process, what is left to do?
We're in the process now of finalizing site selection, finalizing the startup of those sites. We'll dose a patient next year, and we'll be open with the public about that event as well. We think there's a really positive outlook on enrollment here because of the unmet need. It's an in-office procedure. That will facilitate getting patients through quickly. The study is designed to have a phase 2B where in the phase 2A, we dosed maybe 15-20 patients per arm. Now we're talking about 2x-3x that. We'll be more detailed about the design as we go forward. That will roll directly into a pivotal offering analysis. That will also kick off a second pivotal at the same time.
There will be a readout, and then these patients will automatically roll into the pivotal and concurrently. Is that the way you're envisioning?
Yeah. Those patients will be part of the pivotal data set ultimately. Yeah.
At what point can you come back and start actually communicating with investors and analysts around what that transitional studies look like?
Yeah. We haven't specified a date for that yet, but we'll be more once we get the study up and running and we see the enrollment trends, we'll be giving more guidance on expected dates for expansion into the pivotal, etc. I do want to remind that there's a $100 million milestone for dosing the first patient in the 2B study. That is really critical in terms of cash runway. We're expecting that to be early next year. That is for the first part of the study. Once we have the second part into the second pivotal, there's another $100 million associated with that as well.
That's great. Team, how much read-through will there be from the Wet AMD subretinal program to the diabetic retinopathy program?
I think they're a bit different in the type of disease, the severity of the disease. The dose is higher, for example, in the Wet AMD study. I think in general, they're using the same base product, but in a very different way, both dosing in immune-privileged areas. We've put safety as the top requirement for any retina study. Efficacy has to come with that, which we've got both, we think.
Okay. Very helpful. And team, what is Mitch sort of the cash position of the company and what does it entail to sort of fund a very big year ahead?
With the cash balance that we have at hand, it will get us to the early parts of 2027. What's not included in that figure is additional non-dilutive financing, which includes potential monetization of a PRV that's associated with 121's approval. That's been going for north of $150 million recently. The $100 million for the DR first patient dose was early to receive early next year as well too. All in all, that could get us deep into late 2027, if not even early 2028.
Great. I think also these big catalysts are going to be key inflection points of the stock that is generating a lot of interest because I think if you look, it's been up over the last quarter over 100%. What are maybe, I know since we have like three minutes left and you guys did a great job covering all our questions, clearly, investors listening to the fireside chat are in this room. Everybody's looking for next big year. It's very clear with an approval and two pivotal studies reading out, this is the time to own Regenxbio, right, and do work on the name. What are maybe, some of you guys have been the pioneers in this space, what are some things that you guys feel like investors haven't given you credit that really is going to come to fruition in 2026?
I think just like biologics, gene therapy has had its ups and downs as it's emerged. A lot of the downs have been around safety. We've been working for years and years on immune suppression regimens and applied what we learned to the Duchenne program. It's enabled us to now maximize the dose as opposed to having to hold back and maybe not give the full benefit to a patient. I think it's that institutional core business that what we do is gene therapy, and that's all we've been doing for 15 years. Early on, we did it through licensing, but then we took on our own development. The core knowledge of how to make, how to dose safely, and how to design a program to maximize benefit for patients all resides within our walls, which I think is exciting.
I think that we've always been, I think, very transparent about our data. That's something we will continue as we become a commercial entity to talk to people about how the products work, how they're designed, and how we make sure that safety is top of mind.
Great. Team, it's wonderful to kick off the conference with you this morning as my first fireside chat. Really looking forward to a great year ahead of us. Thank you again for being part of our day. Let's give a big applause to the team.