Welcome to day two of the 2024 Bank of America Healthcare Conference. Thanks for joining this session with REGENXBIO. My name is Alec Stranahan. I'm Vice President and Senior Biotech Analyst covering REGENXBIO here at BofA, and I'm pleased to be joined today by Ram Palanki, EVP of Commercial Strategy and Operations, as well as Paulo Falabella, VP of Clinical. Thanks for being here, guys.
Pleasure to be here.
Thanks for having us.
Great. So I think we'll just, you know, jump into the Q&A. I've got a few here. If there's any questions from the audience, feel free to raise your hand throughout, and someone will be around with a microphone. But, you know, maybe, guys, just to start at a high level, you know, what's the current focus for the pipeline, and, you know, where do you see you guys differentiating yourselves from other gene therapy companies?
It's, I think, coming into this year, like, we've become a pivotal stage, pivotal stage company that's moving towards potential BLA submission this year and becoming a commercial organization in the near future. We are the only company that has two pivotal programs now in a public health priority with wet AMD. We recently announced that, you know, we're making plans to go into a second pivotal trial in diabetic retinopathy, which is also a public health priority. I think those two programs combined together puts us in a very segregated space from the rest of the gene therapy world that's been focused on monotherapy and monogenic gene therapies for rare diseases. We're the first ones that are carrying this forward on the basis of a pivotal program and getting closer to commercialization.
And on the heels of that, we are also about to submit, our BLA coming into the second half for MPS II, which is a rare disease. And I can have Paulo speak to some of the data set, as we go through the Q&A. I think all of those combined together with our manufacturing capabilities, that gives us, the ability to move products commercially and, and on a development basis really quickly through the process, and install them early enough. So as we're thinking through the commercialization risks, we are kind of addressing them upfront. So that's kind of where we are as an organization today, and, and very excited to be, sitting here and having the rest of the chat with you.
Yeah, fantastic. That actually feeds into my next question. You know, NAVXpress, that's your platform for manufacturing. How do you see this as a differentiator or maybe a moat, for you guys, having this now fully built, built out, and, you know, how do you plan on leveraging manufacturing going forward?
Yeah, it's... We've been very thoughtful about the capability of manufacturing in gene therapies, generally speaking, and I think, we've been leading that effort from day one. As we came into the last five years, we've invested a lot into building our own facility, all the way to ensuring that that facility is scalable to supply the gene therapy concept, not just for rare diseases, but, you know, things like public health priorities, as well as high-dose indications like Duchenne, right? You need a lot of efficiencies and on the basis of yields, purities, and the commercial process that needs to be carried on early into the clinical development, so you can come on the other side to compete.
I think we have really set up ourselves to be in a place where that capability really differentiates us from everybody else, on the heels of gaining four pivotal programs and a BLA submission.
Right. Yeah, definitely no shortage of things going on in the pipeline. Maybe we can actually start with DMD, since this is, it looks like it's entering, you know, what could be a pivotal study, later this year. You provided an interim update in March and then additional patient in dose cohort two last week, I think. How did this build upon the data you've shared previously, and, you know, how should we be thinking about the next data update in the second half?
I'll just set the big stage and let Paulo actually speak to the data itself. I think the data set that we have recently brought forward really helps us to make a decision on a confirmatory basis to carry the dose level two forward. We have announced this publicly as of the earnings call, that we are going into a pivotal program coming into quarter three, quarter four this year, and Paulo can give some more details around it. I think it really sets the stage for us to come out and differentiate ourselves for an age group that our competitors haven't been able to show data on. The construct is clearly bringing forward data sets that we believe have a differentiator.
Our construct is very close to the natural microdystrophin functional components, as well as the attenuated form of the disease, which is Becker's. It's showing that on a clinical basis, the preclinical data is transforming into what we expected, and that's the conviction that's carrying us into phase three. Paulo, do you have anything to add?
Yeah, I mean, first of all, starting with the safety profile, I think we can't take for granted. This is a space, pediatric condition, with high levels of gene therapy, and so our safety profile has been extremely positive, and we definitely don't take it for granted, and across two dose levels. The other part is, on the efficacy front, we're seeing consistency in high levels of microdystrophin, regardless, you know, of the age group, and to our knowledge, we're the only ones that have shown this so far. Double digits in microdystrophin in patients that are eight and 12 years of age, this is what's giving us confidence to move now forward to the pivotal phase.
Okay.
Yeah.
That feeds into my next question. You know, I guess, what are you seeing at dose level 2 now, that's driving your confidence to select this as the pivotal dose?
... So, so a couple of things, right? So even in the preclinical work that we did, we saw that dose level two was clearly showing benefits versus dose level 1. We see now that the safety profile in dose level two is the same as dose level one, so it doesn't influence our decision there. And now, again, if we look at the age group that's missing data, even according to regulators and Peter Marks' statements, the older age group is the one that's really missing... There is a gap of knowledge there, and I think our construct, and also not to forget to mention that our construct is the one that's closest to the natural microdystrophin, the natural dystrophin protein-
Mm-hmm.
-which has the C-terminal domain. So all these components together, if you look at the level of the consistency that we have in micro dystrophin, especially in the older patients, that made us, you know, very confident in moving forward with that dose level.
Okay. As it relates to the pivotal study, do you feel like you more or less got a good sense of how this could look? It sounds like you've had multiple interactions with the FDA, or are there still some things that you're ironing out, based on your latest feedback, in early 3Q?
We, we have ongoing communications with the agency. Now we're taking the next steps. We're in the phase two, and we definitely have a good understanding of what that pivotal looks like. You have all the functional measures and strength and time tests to support the package, but the primary endpoint would be micro dystrophin. So we're looking at using the accelerated approval pathway as our strategy, regulatory strategy.
Right. I know one point of investor pushback, and I think this may be a misnomer, but if there's an approved therapy for DMD, does the accelerated pathway still stand for you guys? Any feedback there?
Yeah, and I think it goes back to differentiation. I mean, that's how the agency looks at this. So I think if you have, if you take a look at our differentiation in the construct and in the age group, that so far the only product that's. And now, of course, we're waiting for the final feedback from the agency on Sarepta's construct. But, we are offering definitely a differentiation in the efficacy for that age group that they haven't shown so far. So we believe that the road's still open for us. And also not to mention- sorry, I know I see you going there.
No, no, go ahead.
There is a group of patients that will have antibodies against the other AAV that also we will be the only options for them.
Right.
Yeah, there's a serotype exclusivity and patients that don't qualify on the other end. And I think the data that we've shown so far is so compelling, in the context of even how patients would wanna choose these therapies, even on the heels of commercialization that's coming from a competitor. I think there's going to be a lot of discussions between the families, the investigators and the patients to really figure out what's the right thing to do in different age groups. Again, going back to the concept of accelerated approval, we've been engaged in conversations with the regulatory authorities, and we think that pathway is gonna stay open no matter what the outcome is.
Hmm. That's great. And, you know, to your point, you're recruiting patients into AFFINITY-BEYOND, as well, which is a separate study. Is there an expectation that a subset of DMD patients could have an AAV8, you know, pre-existing AAV8 immunity, that could lower the efficacy of 202? Or, is this not really a big factor?
Oh, I can answer that. So, so far, our studies have only evaluated patients that are anti-AAV negative.
Mm-hmm.
So we don't have yet data on that. We haven't explored that yet.
Mm.
Some companies use, depending on the threshold, what you call positive or negative. Maybe there will be areas to explore for us, but so far we don't have data to speak to.
Okay. But that study will be helpful to get a broader view, right? Of-
Yeah, I mean, AFFINITY-BEYOND is more a serotype prevalence study that shows us patients, I mean, how many patients might be excluded due to antibodies. Not yet to the point that we can speak to efficacy. We'll have to run an interventional study for that.
That study also helps us to identify patients that could be coming into the pivotal trial too. It's been a whole strategy around how we structured it, just to understand seroprevalence, but also in the context of helping to expedite the recruitment process.
That has been a major driver for us, yeah, in terms of efficiency, 'cause then, a family that's particularly interested in the study, they can go into that, protocol and just find out if their child is eligible or not based on antibodies, which is-
Mm
... can be an exclusion, a major exclusion for the study. And then, upon having that data in hand, they can decide to go into the study. And so efficiency in recruiting has been paying off for us for sure.
Okay. Very interesting. You know, for DMD, I think probably the latest, you know, broader development news, there's a few competitors, but I think most notably was Pfizer, who reported a patient death, unfortunately, on their DMD therapy, I think last week. Any high-level thoughts on how you differentiate amongst different approaches for DMD, either, you know, on the efficacy or the safety side or both?
Do you wanna-
No, no.
Technical details, and maybe I'll share some.
Yeah, I mean, as I think I said it before, like you should never take for granted, right? You talk about pediatric condition, which has its own comorbidities... high levels of AAV. The fact that, I mean, our safety profile has been pristine so far. I mean, and, that speaks to, we believe, to the construct, but also some proactive measures that we did in designing this study. So we use a prophylactic, immunosuppression regimen that we believe that's also, responsible for what we've seen in the clinic. So a differentiator on the safety for sure. On the efficacy's construct, that it is different than the other ones that have been introduced in the clinic. It's the closest one to the natural, microdystrophin, the longest one.
And now I think we're starting to see the microdystrophin expression, robust expressions that we see in the clinic. A couple of months ago, one of our investigators at the MDA conference presented some just early videos from functional assessments in some of his patients, including a 12-year-old. And what you see that, again, it's preliminary, and we're looking forward to the second half of the year to present more functional data because I think that's when you start to separate yourself from the pack.
Mm-hmm. I think on a big picture, you know, you look at the Pfizer program. I think they've had lots of safety aspects evolving over time, and it's been consistent with that construct. What we have shown to date, and I think is consistently showing the efforts we've took in building the construct to the way we have actually installed the clinical program, even on prophylactic immune suppression, is all moving us in the right direction. You know, it's never good when a patient dies in the clinic. I think on a big picture, this probably creates more space for us as a competitor now right behind potential Sarepta's enlarged label that we are all waiting to see what it's going to be.
Mm-hmm.
I think we have few advantages here. You know, the age group we are operating in, nobody's been able to show those type of outcomes. And then when you think about the ambulatory patient population, 50% of that population is 8+. And again, another 20% is below four. So 70% of the market is actually the patient groups that probably haven't been studied properly and don't have data to support the existing landscape.
Mm-hmm.
We have generated data that really gives us confidence that on an efficacy basis, on a safety basis, and you combine it with the COGS we have on the efficiencies we've created, even as we come on the other side, outside of prevalent pool, when this becomes 100% incident market, I think we have a chance to really bring forward a product that really wins on all those three concepts.
Mm-hmm. That's great. And Ram, you know, you mentioned the Sarepta label expansion to the older DMD patients. Any high-level thoughts around that? And I guess, what are you guys doing for your own program to position it to have data that directly addresses those older kids?
Yeah, I mean, we have already been focused on generating data in older patients, right? And you've seen the data that we put out there, and no, in our knowledge, that data hasn't been shown by our competitor to date in that older population.
Mm-hmm.
Again, to Paulo's point, it's not just expression, but it's expression that's considered to be consistent across age groups. You know, we hear consistently from investigators that the double-digit expression really gives them confidence that you will see these functional outcomes on the basis of consistency. Of course, there are differences on function on age group, but generally speaking, that gives them a lot of confidence.
Mm-hmm. Okay. Okay, that makes sense. I wanna switch gears here to your ophthalmology, the 314. You know, maybe to start, this is your AbbVie partnered program now. They're, you know, eagerly awaiting the wet AMD readout for subretinal. There's plans to take suprachoroidal forward in DR. I guess maybe at a high level, how is the AbbVie partnership structured, and, you know, how has that relationship been to date?
Yeah, the basics of the construct are it's a strategic relationship. You know, we announced this coming into late 2021. AbbVie is responsible for global commercialization, and development of the asset, and the pipeline assets, meaning DR and wet AMD. But the construct on the U.S. side is we do everything 50/50. So it's a 50/50 partnership on cost and profits. Once you step outside of U.S., it's high teens to low twenties in royalty streams, and they take care of all of the 100% of the efforts on a development and commercialization basis. And the split on overall development costs is two-thirds AbbVie and one-third us. So that's those are the basics of the construct, and obviously, we've retained majority of the economics in the largest market. When I say majority, on a 50% basis.
Mm-hmm.
That's really the construct that's been designed to make sure that, you know, we have a product that's addressing public health priorities in wet AMD and DR. A partner like that, that has a commercial infrastructure in 170+ countries, not just commercial, but a development infrastructure and a regulatory infrastructure, it really helps us to accelerate the whole process. I think you know this, we've announced that we're on track to submitting global regulatory submissions in first half 2026. I think that's the advantage of having a partner like that, that our program now evolved to be on a global basis, and we can accelerate the access to product on a worldwide basis very soon.
Mm-hmm.
For the suprachoroidal programs, this is also recent announcement. The DR program is in the process of planning towards moving into a pivotal in first half 2026. We believe that is an unmet need that no other product or product profile can address, that we bring to the table on a very unique basis. And you know how many people have diabetes across the world, and just in the U.S., I think it's about eight million people. And in the clinics, there are hundreds of thousands of patients in the retina clinic today. They're simply being monitored because clinicians want to treat them, but they don't have a product profile that they can use.
The concept of a one-time treatment in early diabetic retinopathy, where you can stop the disease in its tracks from progressing to these vision-threatening complications, where it becomes too late to manage these patients, or you have to manage them on a lifetime basis, that is a very attractive product profile for clinicians, and payers.
Yeah. Right, that makes sense. I mean, you mentioned, you know, having AbbVie as a launch partner is really an asset to. That's, that's the kind of scale that's difficult to achieve, right? And there's other gene therapy companies developing wet AMD assets that, they're you guys are obviously at the forefront, but they are there presenting data, but they don't have AbbVie as their partner, right? So how does that sort of create, you know, maybe a competitive moat for you guys, and, you know, how does that help you not just compete against other gene therapies, but against, you know, the entrenched anti-VEGFs?
It's, I think I talked about the capabilities and the extent of geographical footprint that AbbVie has. And with the acquisition of Allergan, they also acquired a lot of the ophthalmic capabilities on a worldwide basis, not just, you know, what they've been operating in immunology and neuroscience, right? So that really puts us in a very unique position because we think about not just, you know, a study design from a standpoint of getting regulatory approvals, but how do we get these paid in the most optimal fashion and derive the entire value of the asset, and also considering the local country dynamics on the basis of market landscape and local payer challenges, all the way through the local regulatory aspects. So we think through these very proactively.
So when we get there, this is a global launch, not just a US launch. I think that just gives us very distinct advantage on how we implement this, where we have years of lead time on everybody else-
Mm-hmm.
in establishing with the subretinal program, a gene therapy infrastructure commercially, that is well entrenched into the community, and coming behind it with something like DR, with the in-office procedure, that just makes the whole process very efficient. And then, you know, we have a suprachoroidal program in wet AMD too, that's intended to take the procedure into the office because we know that will lead to broader adoption and, and a larger market, so.
Yeah. Yeah, maybe we can talk about suprachoroidal a little bit. So you recently reached alignment with AbbVie to move suprachoroidal 314 in DR, specifically forward to pivotal study in the first half of next year. Maybe walk us through the data points that triggered this, you know, the emerging data or the data we've seen and, you know, how a pivotal program in DR could potentially look.
Yeah, it's. Again, we went through this process a few years ago, looking at DR and where else can we take 314. And when you think about diabetic retinopathy, you know, it's a disease that starts early on with a very asymptomatic piece of the disease progression, where you see these changes in the retina, but patients have good vision, but they haven't gotten to a place where they develop macular edema, you know, proliferative disease, which is called PDR. There's also another complication called neovascular glaucoma. All of these are a reflection of the progression of the disease, and there's very good established data to show what the risk of the progression is once you're at a stage of diabetic retinopathy on a one-year, two-year, three-year, four-year, five-year basis.
Mm-hmm.
So the concept we've took, because, you know, think about a gene therapy that could be administered early in the disease process, so these patients never develop these symptoms. So you're preserving the maximum function in these patients and also not letting them to come to a stage where now they need these lifelong treatments to manage them on a chronicity basis. So I think with this concept, what we are trying to do is really have a disease-modifying effect in diabetic retinopathy and bring a whole new treatment and then create a whole new market, like what's been happening in dry AMD recently, right?
And I think it's also a perfect space for gene therapies to operate because these are asymptomatic diseases that have to be treated for their lifetime, and if you can actually stop the progression of this disease in an early stage, you will preserve a lot of value for patients and healthcare systems.
Okay, that makes sense. And Ram, you know, so suprachoroidal DR is moving forward. You have AAV, suprachoroidal wet AMD ongoing. You know, what's sort of the gating here to also move this one forward to pivotal? Is it waiting for the subretinal data? Is it something else you want to see from AAV8?
You're talking about suprachoroidal wet AMD?
Yes.
I mean, we've announced publicly that we will give an update in third quarter this year on that data set. Obviously, you know, a pivotal decision comes with, you know, we feel like we've reached a dose level that maximizes and extracts the value of 314 on the basis of risk and benefit.
Mm-hmm.
Yeah, it's, you know, when we see that, we would want to move ahead with that process. We've seen that in diabetic retinopathy now with dose level two, and that's really what's led us to get to a place where we shouldn't be wasting time and taking this forward.
Okay.
Yeah.
Okay, that makes sense. And, you know, you've got your own internal pipeline, you've got the AbbVie partnership, but you also have outlicense to Ultragenyx and others. Maybe specifically on DTX-401, I think Ultragenyx is guiding to data this quarter. You know, how, how much of an impact, this is a phase III readout, so how impactful would this be for you guys as they read through?
... I mean, Alec, this, these were historical licensee deals we have done when the company was focused on licensing the technology, versus today, we are a product company that's focused on moving our products to the market. So, we have never publicly guided to any of this or publicly disclosed what it means, but I can tell you what our focus is: our products, not the licensee outcomes.
It would be, I guess, a nice, because there is some economics if it does get approved, right?
Yeah, again, these are all historical deals.
Yeah.
So it's, you know, the focus then versus what we have today is very different.
Okay. And maybe just on cash as well, you recently completed a $140 million raise, which added to your 4Q cash position. So I think, you know, runway is now into 2026, is the latest guidance I've seen. Some big events anticipated that could trigger, you know, milestones from AbbVie next 12-18 months, and I think you could also be eligible for a PRV from 121 as well, right? Which we haven't talked about. But, you know, are these factored into your guidance at all?
No, the $200 million milestone that we are contractually supposed to receive when the phase 3 actually kicks off for DR. And the potential PRV that comes from the approval of 121, neither one of those are included in the cash guidance today.
Okay.
Yeah.
Okay. And maybe we can just touch on 121 a little bit, give it a little bit, of time in the sun. And then from that, maybe you could just talk about what you're most excited about, just broadly across the, the pipeline in terms of, you know, catalysts next twelve months.
Yeah, I mean, RGX-121 is an exciting catalyst for us from a standpoint of the organization going from, you know, a clinical development organization to, you know, shifting towards a BLA submission and laying foundations to become a commercial organization. It really helps us to think about, you know, the set of things we have to do now on what we have to stand up coming into a process for BLA submission.
The most exciting part for me, and I came to REGENXBIO six years ago, and I followed RGX-121 as a journey and, the product profile that we thought we were going to accomplish in terms of neurocognitive function, restoration and preservation in kids, it has actually exceeded our expectations in the clinic, you know, with the dose level three data, which is the pivotal data that we're submitting to the FDA. What we have seen is actually, with a single treatment, these patients are also coming off of enzyme replacement therapy for their systemic disease, right? So them coming off of ERTs with a treatment that was designed for mostly addressing the neurocognitive function, really transforms the concept into a true one-time therapy now for these patients.
It has a huge implication on the socioeconomic impacts of treating this disease, and the cost of treating this disease with ERT, versus a single treatment that can address both neurocognitive issues and help these patients survive without any enzyme replacement therapy. So I think it's a big shift in what we went into this as a TPP versus what we're seeing coming out of the clinical data. It has a very enhanced profile, and there's a lot of excitement in the patient community to access this drug, so we're excited about it. And then going into next year, and then we literally have two pivotal studies that are recruiting today in wet AMD.
You'll see readout from that pivotal program next year in wet AMD, and we're going to start a new pivotal program in first half in diabetic retinopathy, both of which are public health priorities again. So it's getting us closer to becoming more of a pivotal stage company in large, chronic, prevalent conditions and setting the stage into rare diseases. And on the heels of this BLA submission, we've also announced a pivotal trial in DMD now coming into third quarter, fourth quarter this year. So coming into next year, literally, there are four pivotal trials that are running into the next two to three years, being very transformative for the company.
Great. Very exciting times for Regenxbio. So unfortunately, I think that's all the time we have, so we'll have to leave it there. But Ram, Paulo, really appreciate the discussion and for your participation. Thanks a lot.
Thank you.
Thank you.