REGENXBIO Inc. (RGNX) September 2026 Conference Transcript

I'm one of Baird's senior biosec analysts. I have with us for my first fireside chat of the session, Regenex Bio. There's a company that I do cover, big fan of. They're working on a number of gene therapies. I would say they're more or less like the preeminent gene therapy company out there as far as AAV gene therapy goes. So we're going to walk through the story. They have a number of clinical programs, very late stage at this point. a couple of potential approvals over the next two years, more than a couple. So, you know, maybe just to kind of get things kicked off, it would be great if you could just kind of give us a very high-level overview of, you know, what's Regenexx, what do you guys do, what's sort of, like, the core competency, and, you know, what's the value of sort of, like, your AAV platform?

Yeah, glad to be here, and thanks for the invite. We've been in business for roughly 15 years. working on AAV, primarily AAV8 and AAV9 as the base capsids that we've been innovating on. The company is really divided into two different areas. One is the retina programs. We've got Steve here, who's an expert in retina, that can speak to that. And then the other is the rare disease programs, which is primarily near-term, the Duchenne program, which we started a few years back. And then behind that, we have the Hunter program that we're still working on an active BLA. So we have a broad set of indications, broad set of ways to deliver AAV, and probably I think the lead on how to deliver safely, which has always been a concern around AAV over the years. I think we've really leveraged all of the institutional knowledge gained over those years and really applied it to our programs.

Great. So maybe we'll start with the Duchenne muscular dystrophy to kick things off. I mean, And this has been a hot and cold area for, you know, the entire time I've been covering it, which I think goes back almost 15 years at this point. There's been a number of therapies approved. There's been a number of disappointments in terms of clinical trial data. Talk to us about RGX202, your DMD gene therapy. When you kind of compare and contrast it to the other gene therapy on the market, Elevitus, you know, what do you see as sort of the key advantages here? And, you know, in terms of the design of the dystrophin itself, in terms of the vector and the CT domain and what that could potentially mean in terms of functional benefit.

Yeah, I think there's several pillars in the design that differentiate our product. One is the core design of the construct that includes the C-terminus, which is naturally present in full-length dystrophin. It's been incorporated into our microdystrophin. And early on in preclinical studies, we could see it behaving differently and able to affect, actually repair the muscle, as opposed to just enabling the muscle to show force. So that's a huge differentiator. I think also the purity level of the product. So we have been working on AAV manufacturing for over 10 years. We're probably the only company to be able to make high-dose AAV at 80% full capsid, which I think is extremely appealing to FDA. And particular to Duchenne, Steve's team really looked at other, I think, technologies that evolved in transplant, for example, where we used a modified immune suppression regimen to enable us to deliver safely this high-dose AV and give patients the best possible chance at functional benefit. So early on in the program, we could see right out of the gate that our SAE rates were much lower than the currently approved program. And then over time, as we've accrued additional functional data, we've started to see this really large magnitude of effect from patients versus their baseline levels that really is differentiating on function as well. And alongside of that, more at the biomarker level, very high levels of microdystrophin, very high vector copy numbers per cell, which we hope will translate to long-term durability of effect as well. So we really, we love the data that has been created, The top-line data, we think, was really compelling. Everyone that we've shown it to, investigators, patient groups, all really are supportive of it. And so our sole focus now is to move that towards the BLA submission and potential approval next year.

So one of the things that we've sort of been very impressed about on the dystrophin expression side of things is not just the depth of microdystrophin expression that you're getting, but just the consistency compared to Elevitus. You know, I know in the FDA review they had slides showing, you know, a fairly large percentage of patients are at, like, very low levels of expression. You know, you guys have shown some interesting data. Can you talk a little bit about how you have presented sort of the expression correlation with functional benefit out of the patients they've treated so far?

Yeah, absolutely. Maybe I'll let Steve take that one.

Sure. And I think that's one of the numerous differentiators that we see from our data package. And I think one of the key aspects is, you know, just to presage that is all of those safety benefits are what allow us to get to an optimal dose. and we believe that's key for differentiation not just on safety but also the efficacy and it may be or it actually makes sense and if you only have a modest efficacy benefit you may not be able to show correlation so for us the consistency of the micro dystrophin and also translation of that into consistency on functional benefit has been a key story and And related to that, particularly for accelerated approval, that translating into actual correlation. So that's always been in our statistical analysis plan, and we've actually shown that. So based on looking at NSAA correlation to microdystrophin, we've seen not only a high statistical significant correlation, but what's important is it's a very strong correlation. So if you look at the correlation coefficient, it's roughly 90% or 0.9, I should say. And that's much stronger than what's been seen previously. With some cuts with Elevitus, there's a very small correlation.

The Peter Marks cut.

Yeah, Peter Marks showed that. And it shows there's an interest in that from a regulatory standpoint. point, but that wasn't viewed as compelling because of how weak that correlation was, and that's why in the label it's very clear that clearly stated that there's not a correlation. The other thing is we see that consistently across the different ways of looking at an SAA, whether it's propensity score weighting, which is the key primary, but also external control matching or CTAP approach so that's based on the top line cut that we did that we presented earlier this year and we look forward to having that data with a larger data set as we advance and have the the full data set for the pivotal study great so we just touched on Peter Marks but the DMD space has been like one of the hot button topics in regulatory overall.

We've seen a lot of leadership interventions in DMD reviews over the last 10 years. We have sort of new leadership in CBER right now and you guys are in the process of submitting or planning to submit in the very near term a BLA for 202. So maybe just walk through us where regulatory discussions are and like what stage you're at in terms of planning for BLA submission and what those next steps are and relative level of confidence in how the regulators are looking at your package.

Yeah, and this is where I think the Hunter program is a little bit intertwined with 202 in that we just submitted a BLA for Hunter. And so from an organizational standpoint, we know how to do that. Again, for Duchenne, we have the nonclinical section of the BLA already complete and ready to go. CMC and clinical are going as planned, so we'll expect to do a Q1 submission. What's a little bit new is we've had back-and-forth discussions with leadership at FDA. They want to see the data, and so we're very eager to bring the data to them. So we'll do a pre-BLA meeting late this year with FDA to go through it. If you think about it, the last time FDA saw our data was in the end of Phase 2 meeting. We have about ten times that amount of data. We had five or six patients back then. We have 63 treated now. So this will give us an opportunity to show FDA basically from the most recent data cut what will be filed in the next quarter. So we're really excited to see that. And I think we see, to your question about new leadership, strong support for accelerated approval and understanding of the unmet need in Duchenne, because the prevalent market continues to grow. There's a pretty narrow administration of the approved program, approved product. And so we see a great fit for our program as we move forward and an urgency for it.

Great. So maybe that's a nice segue into the confirmatory study that you're running, Affinity. Can you talk about the design of that study, when you expect data from that study, and to what extent you believe FDA is going to take confirmatory study into consideration as it begins to comb through the BLI?

Yeah, I think certainly the confirmatory study, and I'll let Steve talk a little bit about the design, was actually part of the original protocol that FDA reviewed. So both the PIVOTAL and the subsequent confirmatory study were outlined, and the approach was outlined in that protocol. I think, importantly, when we finished enrollment of PIVOTAL, we went straight to enrolling the confirmatory. So we've completed enrollment on the confirmatory study, And I think that will be favorably viewed in the review process. I don't know if you want to talk through the design a little bit, Steve.

So a key aspect is this was, from the beginning, always part of the accelerated approval pathway aspect. So as Kern mentioned, I think it's important to note that was always part of the overall protocol that was discussed at the end of phase two meeting. So we got to incorporate any feedback and proceed with finalization of that protocol submitted in advance with the study. So that's always been in there, the pivotal and the confirmatory. The analysis plans for the primary endpoint and the key secondary endpoints has been consistent throughout. and we've also been consistent with the immune regimen that Curran mentioned throughout our early stage pivotal and confirmatory. We wanted to have a broad population so we have one plus years of age in there and also a relatively broad population in terms of mutation status. So we only exclude the 8, 9, 10 deletions and otherwise it's wide open. So very comprehensive, 30 patients, and looking at function out to two years as a means to confirm the reasonably likely to predict clinical benefit from the pivotal study. We haven't given specific guidance on when we'd have results from that. And I think it's also important to note that that's really confirmatory. We've always said with the FDA, we'd provide data from those patients that we would have as far as safety, for example, which is as far out as you'd expect for these patients. And I think another important point is we started rolling this right after we finished enrollment of the Pivotal, and we completed enrollment very, very quickly. So the benefit of that is we're not just going to have some follow-up for safety. we're going to have follow-up beyond that initial three-month window when you expect to see safety issues. So we think that's a pretty compelling safety package to come in along with microdistrophin and the functional data that we'll have from the pivotal.

Great. And then maybe a similar question just for the affinity rise study, which is sort of the confirmatory study that I think the FDA also wants you to do, but it's structured for maybe European approval, which so far has required RCTs. So just with the design.

Yeah, sure. And, you know, our approach there all along has been for global regulatory purposes, since we know for Europe, as you mentioned, that we need a randomized controlled trial. So that's always been part of the plan, and we're happy that we're at a stage where we can advance with that. We've gotten feedback from Europe, so we're confident to proceed with this. So it would be a standard randomized controlled trial. We haven't given a lot of details on this as we make the final touches on the protocol, but I think you can expect it's not going to be dramatically different from the precedent that fortunately is out there for thinking about randomized controlled trials.

And the plan for that will be that it is actively enrolling during the period of review for the accelerated approval. So it's sequence as well.

Great. So maybe we can move on to CERVAC in the not-too-distant future. Very soon we're going to see the first phase 3 data for gene therapy to express VEGF in an ophthalmology indication wet AMD. So maybe you could just kind of like walk through, you know, what Schurtevec is doing and what sort of the goals of the studies that are enrolling with AbbVie are.

Yeah, we just had a meeting with AbbVie last week, really, to plan for top-line data, which is they've already got the shell of the PR written, which is exciting. So that will be a joint release. And as people know, hopefully the studies are significant, two large pivotal studies with over 600 patients per study moving forward. So we'll have top-line data coming out in Q4. And Steve, maybe you can talk a little bit about what we expect to see with those.

Sure. And not only are they large, these are actually the largest gene therapy trials ever conducted in gene therapy. So this is really a milestone, not just for our company, but really for the whole space. And they're also very comprehensive and global. And this has always been the goal of having AbbVie, that we could really take Cervec globally. And that's really been a benefit for this pivotal program. and it really gives us confidence to the question that you're raising about what we hope to see so the the primary endpoint is de-risked in the standpoint that it's a standard approach that's used when you're doing an active control so it's non-inferiority to on-label uh anti-vegf repeat injections that are available, Lucentis and Ilea. And so that's obviously number one, you got to hit your primary endpoint to show similarity to existing therapy. But the ultimate goal is really to achieve that with a dramatic reduction in injection burden. And in our case, also having a proportion of patients that not only have a reduction but don't need any anti-VEGF and all the while keeping disease activity at bay. So non-inferiority but with traumatic reduction. What's the quantification of that? AbbVie and we have always been consistent with this based on a lot of canvassing of retina specialists. So a minimal bar for us is over 50% reduction in injection burden. Now, we hope to get higher than that, and we have confidence in that. You never know, you know, until you have the readout. But one of the benefits we have is we've done several studies here beyond the first in human study. We did a bioreactor pharmacodynamic study where we got to see a much higher reduction in anti-VEGF injection. We also did a FELLOI study, which is an important advantage of subretinal and even supracoroidal delivery that gives you more confidence to inject in the FELLOI. And if you look at the totality of that data, we see more like 70% plus reduction in injection burden. So that really gives us as much confidence as you can hope for, never any guarantees, but that's what gives us an avid confidence going into the pivotal readout.

And so you said that you guys have just had a call to kind of draft up a blank PR. I guess what, can you give us any guidance in terms of like what the thought is on what will be released in the first PR? Would it just be like a simple achieved non-inferiority, didn't achieve non-inferiority? And, you know, because I think to your point, a lot of us want to understand not just the success of the trial, which maybe you may succeed, but not necessarily be something that is commercially super attractive, but if you showed 100% reduction in injection burden, that would be very meaningful. So will we see more than sort of the up-down on success of the study in the initial PR?

Yeah, I think you'll see, obviously, the top-line results and the non-inferiority, but key secondary endpoints as well, because we know people are looking for things like supplemental injection levels and disease burden reduction. So I would expect to see that, even though obviously we're still in draft form. One thing I think really important to point out is we just recently published five-year data on patients that were treated in some of the early studies. And so one of the key questions around, you know, the overall commercial viability is durability of effect. And we're really seeing a fantastic five years beyond what we might have anticipated in the target product profile.

Great. So that kind of is a segue into my next question, which is sort of, right, we've seen a little bit of an evolution with injections. We've gone from sort of, you know, the first day, early days of Avastin and Lucentis monthly to, you know, twice monthly or PRN, ILEA to now ILEA-HD and Vibaismo. How do you kind of, as you sculpt together all the data and the hypothesis around Shurvec, how do you make the case to ophthalmologists to kind of switch from Vibaismo, which seems to be the market leader in new initiations right now, to a gene therapy? And, you know, are there different patients? How do you kind of think of the bucket of patients? Is it, you know, patients who are very uncontrolled regardless of injections? Is that sort of the low-hanging fruit? Or, you know, do you think Avi and you are, like, just targeting really all of the wet AMD patients out there?

I'll let Steve come, but I think it's going to be a mix. I think there are patients who, for example, only reside in a certain area half the year and go to Florida for the other half. and therefore don't get their regular injections. So we've heard anecdotes of those being ideal patients for a gene therapy approach. We definitely, I think, and Steve can speak in more detail, have treated patients with a high disease burden. So I firmly believe that when we see the data, we won't have to say, oh, you've got to treat early or you've got to find patients that have a low disease burden to be included in your thought process of who to treat. but maybe you can share some of the anecdotes you've heard from KOL, Steve.

Yeah, and I think your last point is important to accent with some additional color that we hear and we actually see when you look at the data is, and this goes to our pivotal as well as our prior data, you can't just look at injection burden reduction and visual acuity effect without taking into account how hard to treat are those patients that you let in. And this is important as you think about pivotal data, including TKIs and other therapies that are reading out, where we have the confidence to look at a broader population, not just the so-called easy-to-treat patients based on the data that we've seen and to your your point and we get this a lot not surprisingly and we always have how do you see this fitting in as incremental benefits occur like I lay a HD and importantly of a BISMO and the way we look at it is those are actually validations of what we're trying to do because these are really incremental benefits initially going from every month injection to every other month being a blockbuster now going from every other month to in some patients not all patients being able to get to every three months four months six months so if anything that only supports that the more reduction that you can get especially if it's a much bigger reduction such as even preventing patients from needing any injection that that's really transformative and that's what we hear from the community that distinction and they've really voted with their feet in how they've actually adopted advances like babismo and that is one of the reasons for sure as current mentioned that we wouldn't just come out with the primary endpoint we'd also come out with how tough to treat with these patients and how much of an effect did you have on injection burden. That's helpful.

And then you and Abby are also driving forward. You start a dose in a patient in phase 2b in your supracoroidal administration in diabetic retinopathy. Can you just kind of outline the differences in terms of the procedure between wet AMD and DR and why there's differences for those two indications?

Sure. So DR is a very different indication other than the ultimate goal is to dampen and VEGF activity. And the reason one of the key differences is the goal is not to treat the vision threatening complication like in wet AMD. It's actually to prevent advancement to these blinding complications, and that's really been a significant unmet need. We know that repeat injections actually work, but it's just not really tenable to take a patient who's currently asymptomatic and tell them, oh, what I see in your eyes, I can treat with repeat injections to prevent you from needing injections in the future. It's just not really a value proposition that plays, but if you have an in-office injection procedure like supracoroidal, that's one time, and you can show the kind of results that we've seen in the altitude study before Avian, and we advanced into the phase 2b navigate study, that's a value proposition that makes a lot of sense, and we already have two-and-a-half-year data where we see very consistent, strong effect at preventing patients from actually developing vision-threatening complications. 70% reduction. So we picked supracoroidal because for us we wanted to preserve the key benefit of subretinal, which is not administering in any cavity where you get spread to all types of ocular tissues. So with supracoroidal, you get compartmentalized injection into that space with a simple procedure to optimize efficacy and safety by preventing off-target tissue aspects, which has really been a big problem in gene therapy for ocular indications.

Okay. And then in the last few minutes, I'd love you to touch on that. suddenly this is your gene therapy for Hunter syndrome. This has always seemed like the most straightforward type of gene therapy and should just easily be approved, but it's hit some road blocks there. So can you just kind of talk through where we're at right now with the clinical hold that occurred and then trying to get that resolved and then subsequently refiling?

Yeah, we have clarity now from all the way back to the CRL that was obtained to a type A meeting that we held subsequent to that, where we had, I thought, very strong support from FDA leadership. Basically, we had to commit to two-year data for both biomarker and clinical data, neurocog data for the study. And that is, at the time, was the basis for resubmission. Alongside of that, we had committed to imaging these patients based on events that occurred on 111, which we think are likely unrelated. And in that imaging, we were imaging not just the brain but the spine as well. And we had findings that we discussed with FDA in some of the spine MRIs that we really can't at this point in time decipher if these are part of natural history or if these are potentially product related. And it's going to take us, I think, more time to do the complete imaging on all patients and then also the time course on several of these patients because some of them were treated three to five years ago. and try to definitively outline, is this something that we would have normally seen in natural history? And again, we don't have MRIs with contrast in patients that are untreated. This is a single-arm study. So I think really we're still planning to proceed with the program. We just need more time to get this evolution of imaging completed, and then we'll make a call on resubmission at that point. Okay, great.

Great. And then I see you down there. So you had pro forma cash of $313 million last quarter. Just walk us through, you state that it gets you to 4Q27. Help us think through that cash burn up against the combination of milestones, potential PRV sales, and just outline what are the cash needs going to be and, you know, what are sort of the levers for non-dolutive capital to come in? Yeah, absolutely.

So the cash at hand right now, as you said, will get us into Q4 of 2027. That's very important because the expected PDUFA Day 4202 is around that time frame. What's not included in that is if we do get regulatory approval and submission for 314, that will come with additional milestones. We have not disclosed it. It's not to the same magnitude as the DR milestone which is the 100 million dollar we received a few months ago so it's not in the same you know degree but that would all modestly get us further into possibly even 2028 I think it was very important to actually get us in 20 because we'll have potentially two product launches so commercial revenue will actually get us even further beyond that so that's not included likewise the PRV we have not included that into the cash runway at this moment in time. But I know we're flashing red here, but nonetheless I would say the critical components for the commercial launch is in place as we speak. That was the reason why we did the raise a few months ago when we did because we want to make sure that the XGOS RCT for 202 as an example will get started. Commercial readiness is starting as we speak. So we'll be well prepared as we get into 2027.

Great. Well, exciting times ahead. Thanks so much for being here.

Always a pleasure. Thanks for everyone in the audience.