REGENXBIO Inc. Q3 FY2025 earnings call

1. Curran Simpson discussed strong momentum across late-stage pipeline of gene therapies, including progress in RGX-202 for Duchenne muscular dystrophy (enrollment completed in AFFINITY DUCHENNE pivotal trial, on track for top-line data in early Q2 2026 and BLA submission in mid-2026, commercial readiness plans advancing), RGX-121 for MPS II (positive 12-month data delivered to FDA, FDA inspections of clinical sites and in-house manufacturing facility with no observations, confident in approval by early 2026 with Nippon Shinyaku), and retinal disease franchise with AbbVie (last patient enrolled in 2 global Phase III studies for subretinal wet AMD, progress in diabetic retinopathy program). 2. Steve Pakola provided details on RGX-202's safety and efficacy profile in Phase I/II, enrollment in confirmatory trial, and expansion plans; updated on RGX-121's positive 12-month data and favorable safety profile; gave progress on retinal programs including subretinal wet AMD and diabetic retinopathy. 3. Mitch Chan provided financial updates: cash, cash equivalents, and marketable securities at $302 million as of September 30, 2025, revenues at $30 million for the quarter, expecting cash runway to fund operations into early 2027 with nondilutive financing opportunities potentially extending it further.

No specific product segment financial performance details provided in a way to extract absolute terms and revenue contribution % as required. The transcript focuses more on program progress rather than detailed segment-wise financials.

1. Expect top-line pivotal data for RGX-202 in early Q2 2026 and BLA submission in mid-2026. 2. Confident in RGX-121 approval by early 2026. 3. Look forward to sharing top-line data for subretinal wet AMD in fourth quarter of 2026. 4. Cash runway expected to fund operations into early 2027 with nondilutive financing opportunities potentially extending it well beyond 2027.

No specific detailed discussion of risks and operational failures provided in the transcript in a way to summarize as required.

Q: On the progress here. Maybe first just on 202. Can you help us with when next interactions with FDA will be? And can we get your thoughts on clearly news coming out of FDA that impacts the DMD community with arguably higher unmet need in DMD, but also just on external controls and other gene therapy programs, how are you thinking about the potential for the accelerated pathway for 202 at this point?

A: Thanks, Judah. Yes, I mean, if you think about the progress next year, we'll have top-line data that we pointed to in early Q2. And then we've also guided to a mid-2026 BLA submission. So absolutely, we'll have potentially several FDA interactions. Of course, the key one is the pre-BLA meeting. And based on that timing, we haven't got a specific date set for it, but it would happen somewhere around the vicinity of top line data and preparing to file the BLA. I think in general, we are watching carefully other programs going through FDA and the debate around external controls. We've continued to update our access to some of the same databases, for example, that were used in the ELEVIDYS approval. And I think that when we look at it, one of the things that's striking to me is, especially in our older patients, we're not looking at a marginal stabilization of patient functional outcomes. We're looking at a really significant difference from natural history in which we're matching that patient to, say, 12 up to 20 patients. And so I don't think we're going to be going into FDA with sort of a modest benefit approach. I think what we're seeing in our data is a significant benefit and even improvement in patients that you would expect maybe the best case at their age would be stabilization. So I think that's the strength at which we think we're eligible for accelerated approval. And I won't leave out to date the safety profile of the program. So you think about benefit to risk ratio, and I think we can provide a significant advantage over the product on the market to date. 2.

Q: On cash runway, I guess, kind of when you internally probability weight potential for these nondilutive financings that you listed, can you give us a sense of where those could potentially get you through without kind of bringing in external capital, or how you're thinking about the potential for cash runway if we do layer in some of those nondilutive options?

A: Yes, absolutely. So if you factor in the nondilutive financing options, inclusive of the PRV as an example, and for modeling purposes, if you use the market price, as you're probably well aware of what the prices are for these PRVs, it could significantly get us into -- well into 2027, if not even early parts of 2028. But again, this is all contingent on what the market price of some of these items can go for. Other nondilutive financing, for example, the milestone associated with the DR first patient dose, that we already disclosed is $100 million. So that in itself, you can factor into the cash runway. 3.

Q: Just a quick question regarding the confirmatory trial for DMD. Maybe could you provide an update in terms of the tempo of enrollment? And where do you see enrollment be at the time of filing?

A: Good question. So we've begun enrolling the confirmatory study actually right at the end of October when we completed the pivotal enrollment. And it's hard to predict at this point where we'll be, let's say, mid-2026 at the point of filing, but I would expect us to be substantially through enrollment of the confirmatory study given that, that's prespecified in our protocol as an additional 30 patients. So we'll have to monitor that as we go, and we'll definitely give updates throughout the first half of next year regarding progress. Steve, maybe you just want to comment quickly on high-level design for confirmatory. 4.

Q: So I would just ask one regarding the regulatory part. I know you have 2 programs like DMD and MPS II, you need to talk to the FDA. Just wondering, so for the DMD, when will you have a pre-BLA meeting with FDA? And then also regarding the MPS II, I know PDUFA is February 8. Any additional meetings set up before approval? Maybe any update color you can have in terms of interacting with the FDA, especially after Nicovodon's departure? And any concern regarding agreed upon the accelerated approval path?

A: Sure. Gena, I'll take the second question first and then circle back to Duchenne. For the Hunter program, we're far along with the BLA review. As you know, the PDUFA date was moved to February 8 from the initial date. We expect between now and that decision point to have a late-cycle meeting with FDA and that we're getting messages from the project leader to schedule that. So that's moving along as what I would call business usual. I think it's important to point out on the Hunter program, we're already past our facility inspection, no observations. Our clinical sites have been inspected as well. with no observations as well. And so some of the things that have held up other programs were derisked, if you will, in that process. And the other, I think, area that we interact as we undergo this review is in the information request that we get from FDA. And I think I would characterize those as well as typical requests, some of which in an encouraging way are questions related to commercial aspects of a program, specifications, pharmacovigilance. So the color of the interactions we're having is positive, and we feel positive about the data we provided for that program. And therefore, our confidence is high that this program, and we think patients support that has a really, really important place in therapies. For Duchenne, the pre-BLA meeting will happen between our top-line data, which we pointed to early Q2 of 2026, and the filing of the BLA. We haven't got a specific date for it yet, but somewhere in that time frame is when we would expect to have it. 5.

Q: Congrats on the progress this quarter. Maybe a question on your manufacturing capacity, if you can talk about your in-house capacity. The Rockville site is obviously up and running and already produced first commercial batch. So I'm wondering what is the scale of production volume that the site is designed to deliver today? And what percentage of domestic patients are you planning on capturing with that site, maybe for both the MPS II and DMD, if you could speak to that?

A: Sure. Yes, the manufacturing facility is -- contains a 2,000-liter bioreactor. It's the largest bioreactor that we know of utilized in gene therapy, and we've already scaled the program up to that level. We've been public about being able to produce up to 2,500 doses of RGX-202 per year. And I think keeping in mind that just is what we can do on an ongoing basis. We can certainly inventory, which we're doing presently more quantities than that to have a significant number of doses available at launch. The Hunter program, being an ultra-rare program, I would characterize it uses less than 5% of our overall capacity. So it's not -- we have good yields, good expression, and we have our own internal fill/finish capability. So we can run very efficiently, but it doesn't take up a significant amount of our overall capacity. 6.

Q: Great progress on all the programs. Just on the issue of using FDA natural history as a control in DMD, I guess it's clear that you have both propensity match comparisons and now the CTAP disease progression model. Is that something designed into AFFINITY prospectively? And could that then further support? And is it a measurement that's accepted not only in the DMD community, but also considered as a valid metric from FDA? That's the first question.

A: Okay. Great. Annabel, I think that's a great one for Steve to address. 7.

Q: And I'm going to be different and ask a wet AMD question. I guess, can you opine on the recent M&A and licensing activity for gene therapy and wet AMD? Obviously, we had Lilly Fredberm and 4DMT licensing, and of course, your licensing. So does the Street have it wrong on the level of interest from retina specialists? And where is your program rank as far as level of engagement with these retinal specialists?

A: Sure. It might be good, Steve, to reflect on what we just heard out of AAO regarding gene therapy in general and specifically our program. 8.

Q: Given a recent expectation for a box warning for a competitor product and the removal of the non-ambulatory indication, just curious whether your expectation is for something similar on your label or other AAV gene therapy labels and how you're thinking about long-term development in the non-ambulatory population in general?

A: Thanks for the question. I think in terms of expectations, I mean, I think our track record in Phase I/II on safety has been exemplary. And I wouldn't expect a black box warning of that nature, given that we've shown clearly the incidence rate of any sort of liver injury for us is virtually nonexistent in terms of the data, whereas we're seeing on the label for ELEVIDYS or in their filing that they have upwards of 40% liver injury in the approved product. So I think we don't expect that. In fact, we expect to leverage safety as part of the accelerated approval pathway that we're pursuing. And I think accompanying that is strong conviction that the differentiation of the product with the immune suppression regimen we utilize and the construct and manufacturing purity. Put those all together, I think we have something very different and very exciting to the patient community to date. 9.

Q: I'd actually like to tack to regulatory questions on the EMA side of things. I know EMA has granted 121 the ATMP designation. But I was just wondering the status of any plans for it at the EMA. And also, any thoughts on the potential sufficiency of the AFFINITY Duchenne study for EMA review? Or what else do you think you need to do there? Is your FDA confirmatory sufficient for EMA filing?

A: Yes. We've had some interactions with EMA regarding RGX-121. And I think that what we're typically seeing there is the requirement for a control arm, placebo control arm still seems to be the predominant feedback that we get. Having said that, there's a significant opportunity in named patient sales that would potentially exist of an accelerated approval. So I think that's something that we are carefully evaluating and could be part of our commercialization approach. Steve, do you want to address the Duchenne question? 10.

Q: Just one for me on diabetic retinopathy. A competitor was able to get an agreement with FDA for an ordinal 2-step DRSS change primary endpoint for the pivotal studies in NPDR. Can you speak to how that's informing your discussions with AbbVie on your pivotal NPDR program and ability to adjust that study plan to potentially improve probability of success relative to a 2-step DRSS improvement at 1 year?

A: Yes, thanks for the question. Yes, I think one item off the bat is that the ordinal approach is something people have thought about over time. The prior lead or director of the ophthalmic division had always required a meaningful change in DRSS, with meaningful defined as either 2-step improvement change or in either direction of worse or improvement. So the advance of being able to get more information out of each patient's DRSS change by looking in an ordinal way now with the new regime has come on the table. So it is definitely something我们've been looking at, both us and AbbVie in close collaboration. So I think it gives us more options. Fortunately, what we've seen is we look good in both respects, 2-step improvement, a greater proportion of patients achieving that and also 2-step worsening a greater proportion of patients showing that in a placebo-controlled setting, as well as what you expect without treatment in the real world and other controlled negative control arms. So we think we're really well-positioned to really take advantage of what looks best in our discussions with the FDA. 11.

Q: A quick one on suprachoroidal wet AMD. First, can you remind us how many patients you're looking to enroll at dose level 4 for that study? And now with the subretinal program fully enrolled, do you expect the speed of enrollment for suprachoroidal program to pick up a little bit now with the shifted focus to that program?

A: Thanks for the question, Dan. So SCS wet AMD is advancing. We're looking to enroll 20 patients in that arm. As you mentioned, we reached the quite significant milestone of completing enrollment in the SR wet AMD pivotal studies, the largest gene therapy program ever conducted across any indication. It's a great point that now, with that trial completed enrollment, a lot of the overlapping sites can now focus on the suprachoroidal delivery route. So yes, indeed, we're seeing a pickup in enrollment in that study. 12.

Q: And a quick follow-up for subretinal program, do you expect Abbott to file in the U.S. and EU roughly at about the same time?

A: Yes, I think that's a safe assumption. We haven't got a specific timeline for the filing mapped out. We're primarily focused on top-line data next year, but we would expect a global filing, and we'll be more specific as we get closer about the interval between U.S. and ex-U.S. filings. But they're recruiting not -- the basis of the ASCENT study being recruited in Europe was to enable that to be a smooth process. 13.

Q: So I just wanted to look again at the functional endpoints on 202 and just ask about the powering around those and whether or not you believe there's a certain threshold or, I guess, outcome that you need to see as a bar for success to really kind of put together a definitive answer in front of the FDA that kind of can't be denied.

A: Sure. Thanks for the question. So we are seeing a nice response, both in terms of change from baseline with improvement, even in the older boys, where you might expect just stabilization or worsening, and with improvement, just stabilization. So I think we're in a good position where if we continue to see what we're seeing and what we report on in early Q2 next year, with not only the primary endpoint for accelerated approval, but also the microdystrophin, I think we're going to be very well set up. And that's based on, to your question, looking at the traditional endpoints. So certainly, NSAA, where marginal effect, if any, depending on the age of the patients has been seen previously, and also the time function tests. So the traditional time to stand, 10-meter walk run, time to climb as the traditional ones where there's a lot of data out there, and we have the opportunity to look with propensity matching. So how good of a data do we have to see? Again, if we continue to see what we're seeing, we're going to pass that bar because of the differentiation that we're seeing. And some bars you can look at are not only against natural history, but also there's data and published interpretations of the data on minimally important clinical difference that we're surpassing. And we can also look by age and by baseline status, what's been seen with approved therapy. And that allows us to feel that we're in a good position to have power based on the data that we're seeing, again, if we continue to see what we're seeing. The overall package is important as well. So the benefit-risk relative to that functional improvement, then we go to the safety where, again, we're seeing very good differentiation. 14.

Q: And on your suprachoroidal program, where are you on your understanding of how closely that can recapitulate the amount of vector delivery of your subretinal delivery?

A: So, are you asking if the protein levels match in terms of transgene expression between the 2? 15.

Q: Yes.

A: Yes. I think because -- Steve can comment further, but because they're delivered to different compartments of the eye, it's very difficult to do direct comparison. So ultimately, what we look at is sustained vision and safety. But Steve, maybe你 want to comment further on the differences we see. 16.

Q: Could you comment on your current thinking regarding the pricing strategy for RGX-121 versus 202? And also, how large a sales team do you think你 need for 121 versus 202?

A: Yes. So if you recall, earlier in the year, we signed an agreement with NS Pharma for commercialization in the U.S. And so the pricing decisions will be made by NS Pharma as we move through the approval process. And Mitch can comment, we certainly will enjoy a nice royalty from sales, but the actual price determination will be made by them. We would eventually make the price decisions since we wholly own the Duchenne asset. And I'd say at this point, it's very preliminary for us to state any sort of thinking on pricing until we get closer to commercialization. 17.

Q: With regard to 202, could you please comment on where you think you might see the potentially greatest demand initially as you start to commercialize in 2027? Do you think about it in particular exon skipper experienced patients or just thinking primarily about newly diagnosed patients? Any color there would be helpful. And then second, on -- with regard to your collaboration with AbbVie and 314, how are you thinking about sort of rough timelines for potential Medicare coverage of 314 post approval? And just sort of what are sort of the block steps there involved for gene therapy coverage in this particular Medicare population?

A: Yes, I'll take the first one. I think, obviously, if you look at the inclusion criteria for the study, we're dosing patients and older. So we'll have data at the time of review for potentially a broad label. One thing that we see based upon the public announcements on sales is that the prevalent market really isn't changing in terms of Duchenne. So by 2027, the prevalent market will be something like 14,000 patients. And if you think about eligible for gene therapy, it's probably closer to 3,000 patients when you subtract out non-ambulatory. So at the time of launch, our aim is to have a broad label and really be able to address patients of all ages. But to your point, we do expect that over time, as the prevalent market diminishes, which could be past 2030, is that at that point, we would be in a great position to address the incident market. Most KOLs think early treatment is ultimately the answer for gene therapy, and we'll have the data in hand to support that age group based on the fact that we're already dosing kids right after diagnosis in some cases. I think on the Medicare coverage for 314, that's a question that I'll defer out a bit. We haven't had those discussions with AbbVie. We haven't had those discussions with AbbVie.