REGENXBIO Inc. (RGNX) Earnings Call Transcript & Summary

Sure. So these are ongoing mass studies, so we don't have access to any efficacy results. So this is all based on the same assumptions in terms of efficacy. So again, the increased sample size gives us greater power on the secondaries, but also increases the probability of success on any of the endpoints. We do have the other bioreactor bridging pharmacodynamic study that we have ongoing looking at the original hyperstack process compared to the bioreactor suspension cell-based commercial-ready process. That's an open-label study. And we've presented preliminary 6-month results from the initial 2 cohorts, which are the high dose of each of those. So as far as what we do have access to, we [ navigate ] to look at that open-label study, and it's showing what we would hope it would show, which is a very good treatment response in terms of BCVA with a dramatic reduction in treatment burden.

Okay. Great. And I wanted to turn to diabetic retinopathy. I feel like this is an area that could grow in importance but hasn't gotten as much attention maybe as it deserves. And it looks, given the data you've presented to date, that maybe patients earlier in their disease are driving a greater benefit to therapy. Could you maybe talk about the trial design and whether there's flexibility to sort of go up in the spectrum of treatment to earlier patients?

Sure. So we, to date, have been methodical in thinking of the range of diabetic retinopathy severity to consider and traditionally, we know from precedent a lot of the focus has been on moderately severe to severe NPDR as a relatively clean population to assess diabetic retinopathy severity using the validated approvable scale and endpoints that can be used on that. We early in development, which we've done in various programs, actually, as we use those early cohorts to learn as much as we can. Now is the time in these initial studies to learn. And that's why we've included a range of not just the 47 to 53 or the moderately severe to -- severe to not get too technical NPDR, but also PDR patients. So mild PDR and moderate PDR even, where we expanded to include moderate PDR. So it gives us a chance to look across the breadth but as you mentioned, the results that we've seen to date, I think not surprisingly show a clear proof of concept in that sweet spot of the moderately severe to severe NPDR. And that's important for a couple of reasons. One is that's where we have a lot of precedent that anti-VEGF, if given very frequently, can really move the needle where you have less worsening and patients don't go on to blinding eye complications the way they do without treatment. The problem is clinicians nor the patients are signing up for this because it's just not a tenable approach to sign patients up for repeated injections for the rest of their life when they're asymptomatic. So not surprisingly and as we had always predicted, clinicians are going to just do watchful waiting until the patients actually develop the vision-threatening complications. But with an in-office onetime treatment, that really has the opportunity to change that whole paradigm. So it's great to be seeing the proof of concept within that sweet spot where ultimately, the goal what clinicians wanting, what patients want is to get ahead of it so you never develop the blinding eye complications. That's the holy grail. But you really need a posology or a treatment approach that's actually appropriate. And that's the only thing that can do that, is an in-office onetime treatment approach. So we recently completed the expanded cohorts where we're looking at the next dose level in both the NPDR and the PDR patients. And we saw a great enrollment really supporting the whole value proposition here in the unmet need. And that supports also our ability to have initial results from both of these cohorts in the second half of this year. So it's really going to be a key milestone to see if we can confirm the benefits that we've seen from the earlier cohort.

Right. Right. And maybe one last point on DR. I think most people are focused on wet AMD given it's a large market. You've got your pivotal studies ongoing. But DR, it is underserved historically. So, I don't know, Ken or Steve, maybe you want to talk about the opportunity in DR in terms of the numbers and what would be a competing option, I guess?

Yes. I mean I think it is highly differentiated from wet AMD, which I think is useful and important and a little bit daunting because it's -- we're basically hurtling in a direction of creating an entirely new market. And because between wet AMD and diabetic disease where there's already edema very -- more similar to wet AMD. I think people get really comfortable and familiar with what already exists, what the size of those markets are on a dollar-for-dollar basis and what's new and emerging. And -- but at the top of that funnel probably by, I don't know, a factor of 4, 5, maybe 10 is actually smaller than the diabetic population that would be filtering into this paradigm. I mean -- and so that means for us, actually, DR in the way that Steve has been describing it could be substantially amplifying the product opportunity for RGX-314. And we'd be the only option. I mean there really are not head-to-head competition considerations like we're seeing in wet AMD. The value proposition for wet AMD here is unchanged for us, but it is -- it's been rare in AAV gene therapy outside of rare diseases to think about stepping into a market that has an unmet need this big with biological plausibility that's very clear where you could be the only option of treatment because of the sort of upstream concerns and considerations on both the part of the caregivers and the patients. It's almost like this 314 was actually made for this, Alec. I mean, in certain ways. And that I said to Steve sometimes, I mean, gee, if there was already an intervention that docs could be doing on a onetime basis, even if it was more invasive, they'd probably be doing it. That's what we keep hearing back. And here's something that with suprachoroidal approach in office, I mean, I think we're talking about the top of the funnel being single digit, maybe low double-digit millions of patients. So this goes beyond moving the needle. This could be transformative. Imagine -- and we all know and touch people, for better or for worse in this company, a country that are developing diabetes and to catch them early enough where they can avoid that progression with a onetime intervention in a confirmatory way would be a game changer.

Right, right. Okay. Very exciting. I do want to shift to the rest of the pipeline. So maybe we could talk about DMD first. It sounds like you've ironed out the manufacturing issues that was holding things up. And we could have data, I think you said in the second half of this year, right, early data. Maybe just to start, how is your asset differentiated from day 1 in terms of its design? And how are you approaching clinical studies?

Yes. We've talked a lot about early on in this conversation, the sort of manufacturing product quality, product purity, scalability, reproducibility that's been a major investment. And that applies especially to Duchenne because these are some of the on a per patient basis, some of the larger requirements that we have for making product. And so building on top of that investment, there's been a -- there was a great effort in the last 2 or 3 years at REGENX too, look at reagents that had been created in research labs that had sort of navigated their way into the industrial setting, and we're starting to be studied clinically and really challenged some of the paradigms about whether or not new things had been learned about biology, or new mechanisms could establish meaningful improvements. And this was an idea and a conception by our Chief Scientific Officer who probably across 3 or 4 decades had been involved in gene therapy and muscular dystrophy research with a variety of researchers. And the answer was absolutely yes. I mean it wasn't too much of a surprise, frankly, when someone asked the question, is there something more we can do today that wasn't done 15 years ago, especially when it came to biology and molecular biology. But we had to do it. I mean we had to make the investment and we had to prove to ourselves that there was meaningful differentiation and it could be done in high quality and with the sort of level of manufacturability that was required. So we've got a new domain of full-length dystrophin that's in none of the other existing clinical candidates for Duchenne. It plays an important role in many, many things that have -- along the way we've talked about in terms of recruitment of more biological species to the cell structure, the cell membrane structure to both reinforce what natural dystrophin is supposed to do, but also it improve the function of the overall feature set of this whole complex. And I think that we've taken the biggest step in making the biggest improvement that's still short of a full-length dystrophin, right? It's just not something that we are ready to admit, frankly, even as a field that we can do with AAV. But I think where we are is between that and things that are currently in development also. And what that means is, I think we, with data later this year, have the opportunity to show at similar doses that we can express dystrophin -- microdystrophin levels that are similar to what others have shown, but emphasize that the function of our dystrophin is going to be different, that its potency that its sort of ability to show better long-term outcomes on a potential basis is truly there. And we'll keep working on proving that out with the passage of time. This year is about establishing that we're safe. Our manufacturability is supporting the quality and the purity that we've been looking for to achieve and that the dystrophin levels, microdystrophin levels are where they should be with respect to the doses that we're starting with. And then what we like about again, the phenomena that's occurring sort of in the background or the foreground here is that literally products are being considered for approval right now on the basis of 3-month expression of microdystrophin. And that's exactly the data that we're aiming to show in the second half of the year with respect to the dose levels we're currently studying. So the notion of acceleration and a clear regulatory pathway is happening potentially in real time here with us for us. I mean we're not a bystander here, and we're actively participating with many, many companies in support of this activity on the part of regulators and part of many, many stakeholders advocating for these things to be happening. And we absolutely are supportive of it happening in Duchenne for all the right reasons for sort of improvements in the ability to improve patient care as it exists today. We absolutely think that those outcomes are going to stimulate more investment. And we're a great example of it. We're actually investing in a next generation of a microdystrophin construct because we did believe many years ago that the opportunity for accelerated approval would be there. So it's only going to increase our sort of ability to feel strongly about that with what we see in the next week or month.

Right, right. So definitely some lessons to be learned. Do you guys have any concerns or -- or is it actually a good thing that you'll be able to learn from some of your competitors in 2, 3 years down the road? Do you think it will be a viable strategy to bring 202 to the market given the competitive landscape could be established?

I mean competition is good in general, right? I mean for me, for a variety of reasons. Number one, it's good and important for patients. It drives innovation. It drives, I think, efficiency. It can and should. It's also, I think, good because it's a motivation to think about how to improve. And again, I think we got involved because of things that others were doing and because we thought that there are ways to continue to innovate. So kudos to those people that were already making those investments and have already sort of advanced some of that innovation, but none of us ever expect it to stop and I don't think we expect it to stop between here, an approval, a series of approvals and sort of the changing paradigm of clinical care and commercialization of products in general. The thing about RGX-202 though that is also important to distinguish is that some of the products that are further advanced in development are different in terms of how they present to kids immunologically. And what that means, and we know this from natural history data and preclinical data and clinical data across a lot of exploration of AAV is that some kids may not be able to get some of those treatments on some percentage basis. It's probably a double-digit percentage basis, almost certainly. And probably high double digit, 20%, 25%, maybe even 30% of kids can't get a single treatment because their preexisting immune status says that they're not going to get the same type of effect that another kid that doesn't have that same status might. So an alternative "competition" is necessary there, right? Because in certain ways -- that's actually the easiest transition that we could almost make in the field in a lot of ways, is to maintain everything else the same, but the interchangeable part of the capsid just so that kids could get access to treatment that they otherwise might be precluded from. What I view is that we've done that plus. So I think we want to -- and that's the beginning of an opportunity for 202 without even having proven that we have potential for additional functional improvement or getting into discussions about improvements in safety or quality or cost of goods. But that's -- I mean those features and those benefits are what we're going to hit on absolutely in our development plan, our program plan and our target product profile.

Okay. Great. Well, looking forward to seeing the progress, both in the second half with DR, DMD, and then next year with the wet AMD readout. So I think we'll have to leave it there for today. But thanks, Steve and Ken, for participating. A great discussion.

Thanks for having us.

All right. Thanks.

Thanks.