REGENXBIO Inc. (RGNX) Earnings Call Transcript & Summary

Thank you for standing by, and welcome to the REGENXBIO Interim Data Update from Phase II AAVIATE Trial of ABBV-RGX-314 for Treatment of Wet AMD using Suprachoroidal Delivery, Hawaiian Eye and Retina 2024 Conference Call. [Operator Instructions] As a reminder, today's program is being recorded. And now I'd like to introduce your host for today's program, Mr. Ken Mills, President and CEO of REGENXBIO. Please go ahead, sir.

Welcome, everyone, to our Hawaiian Eye and Retina event. I am Ken Mills, CEO of REGENXBIO, and I'm pleased to introduce our agenda and make some opening remarks. In November, REGENXBIO announced the pipeline prioritization and corporate restructuring plan that will enable us to focus our capabilities and resources on large commercial opportunities where our product candidates are differentiated, can be expedited, and support meaningful value generation soon and for the long-term. Our highest priority programs are: ABBV-RGX-314 for the treatment of retinal diseases; RGX-202 for the treatment of Duchenne; and RGX-121 for the treatment of Hunter syndrome. Today's event is designed to review and discuss the new interim data from our AAVIATE trial of ABBV-RGX-314, henceforth referred to as 314, for wet age-related macular degeneration, or wet AMD. The slides for this event are available on the webcast and later on our website on the Presentation section at regenxbio.com. We'll move forward. On the second slide of our presentation, you will see that today's event may include forward-looking statements. And please see here a full slide of our forward-looking statements disclosure, which can be reviewed at any time. Please be advised that today's call is also being recorded and webcast. On Slide 3 here is our agenda, and today we're happy to be joined by REGENXBIO Chief Medical Officer, Dr. Steve Pakola; and Dr. John Pitcher from Eye Associates of New Mexico; and Dr. Allen Ho of Wills Eye Hospital. Today at the Hawaiian Eye and Retina meeting in Maui, Dr. Pitcher presented positive 6 months data from the AAVIATE trial of 314 for wet AMD using one-time, in-office suprachoroidal delivery. The slides from his presentation are available on our website on the Publications page, again at regenxbio.com. Steve will provide a quick review of the update and then lead a discussion about the data with these 2 retina specialists. And at the end, we should have some time for some question and answers. Before I hand it over to Steve, I want to remind everyone that RGX-314 is designed for the treatment not only of wet AMD, but also diabetic retinopathy and other chronic retinal diseases. So moving on to Slide 4. We believe that there is a multibillion-dollar potential for RGX-314 as a single injection treatment to become a first-in-class gene therapy for wet AMD and the standard of care to treat and prevent the progression of diabetic retinopathy. You can see here the market for treating retinal diseases is estimated to grow to approximately $17 billion globally within the next 5 years. Now we want to point out on Slide 5. We know that there is a gap between the vision outcomes observed in clinical trials of current anti-VEGF treatment options and what doctors are facing in the real world clinical management of a disease like wet AMD. Patients on average lose vision over time with current treatment regimens due to unsustainable compliance and non-adherence. A single treatment with 314 has the potential to close this gap between the clinical trials and the real world outcomes. In our study of subretinal 314, long-term data through 4 years shows a durable treatment effect and the potential of one-time treatment to maintain vision, vision that may normally be lost in the real world setting. So treatment with one-time gene therapy with the potential to prevent disease progression long-term could be the key to preventing vision loss for millions of patients. And now, I'll turn it over to Steve to take us through the data and the conversation with the specialists.

Thank you, Ken. To start off, Slide 6 shows the basic design of the AAVIATE trial. This is a Phase II randomized active control dose escalation trial evaluating one-time, in-office 314 administration for the treatment of patients with previously treated wet AMD. Enrollment is complete for the latest cohort in which patients received dose level 3 and were given short-course topical or periocular steroids before or after dosing. Today, we'll discuss the latest safety and efficacy results from all dose levels up to 6 months, which Dr. Pitcher presented at the Hawaiian Eye conference earlier today. Before diving into the results, a quick scientific refresher on Slide 7. 314 utilizes a novel AAVIATE vector encoding a gene for an anti-VEGF monoclonal antibody fragment with the goal of sustained protein production by the patient's retinal cells, resulting in long-term VEGF suppression. We and our global development partner, AbbVie, Allergan, are advancing 314 via 2 routes of administration: subretinal, which is currently in Phase III global development; and also in-office 314 suprachoroidal delivery, which is in Phase II development for treatment of diabetic retinopathy in the ALTITUDE study, and also in the AAVIATE study for treatment of wet AMD, that we are discussing today. On Slide 8, we see the patients' demography is well-balanced across treatment groups, and of note, there's a high treatment burden in all groups with an average annualized rate of 9 anti-VEGF injections. Moving to Slide 9, Safety. Across dose levels in over 100 patients, 314 treatment has been well-tolerated with no drug-related or ocular serious adverse events, including in dose level 3. Importantly, there were 0 cases of intraocular inflammation in patients who received short-course prophylactic steroid eye drops. Slide 10 further illustrates that the lone 2 cases of intraocular inflammation on slit lamp-exam in the periocular steroid prophylaxis group were very mild and resolved by the next visit without recurrence. While again, no cases of IOI were seen in the topical steroid group. This is actually consistent with what we've seen in the separate ALTITUDE study in patients with diabetic retinopathy, where 0 out of 20 patients who received short-course prophylactic eye drops developed intraocular inflammation. Now, on Slide 11, we move to efficacy. In the 3 dose levels, including dose level 3, stable BCVA and disease control, as measured by central retinal thickness, was achieved. And on Slide 12, we see the stability of function and anatomy was achieved in the setting of a dramatic reduction in anti-VEGF injection burden, ranging from 68% to 80% annualized injection rate reduction, with the highest reduction observed at dose level 3. Slide 13 shows the swimmer lane plot for all the dose level 3 patients at each visit, with the colored dots denoting visits where the anti-VEGF injection was given. To the left of single dose 314 treatment, that is prior to 314 treatment, we see visually the high injection burden in these patients. While after 314 treatment, it's clear that these patients received fewer injections, including 50% of the patients needing no eye injections. And in those patients who received no supplemental anti-VEGF injections, on Slide 14, we see these patients still were able to maintain stable vision and disease control. So, in conclusion, 314 suprachoroidal administration has been well-tolerated, and in dose level 3 with short-course prophylactic topical steroids, there were 0 cases of intraocular inflammation. One-time, in-office 314 administration also continues to demonstrate stable vision and disease control with a meaningful reduction in treatment burden, with the highest reduction observed in dose level 3, where there was an 80% injection burden reduction, with half of these patients injection free. We are encouraged by these positive interim results as part of our global program for the treatment of wet AMD. As we mentioned, these results were presented at Hawaiian Eye today by Dr. John Pitcher, who we are pleased to have on the line with us today. So, John, let's start the Q&A session with you.

Looking at this data set that you presented in Hawaii today, what are your take home messages?

Thanks a lot, Steve. Well, it's pretty clear that this data was well-received by the retina specialists in attendance. It's also very clear to the retina community and our patients that we're in need of more durable and potentially curable treatments for neovascular AMD. Many of my patients are receiving 12 or 13 injections per year and still at risk of vision loss. So in order to create a paradigm shift or revolutionize the standard of care, new therapeutics need a combination of efficacy and safety, and we see that in the AAVIATE study with no evidence of ocular or drug related SAEs over 6 months. And with topical steroids, which these patients used in cohort 6, topical drops, there were no evidence of intraocular inflammation, which I think is really a big point of this study, and again, very positively received today at the meeting. In addition, we saw a dose response with each dose level up to 50% of patients, with dose level 3 not requiring rescue injections in the 6 months of the study.

Thanks, John. As Ken mentioned, we also have the benefit of having Dr. Allen Ho from Wills Eye in Philadelphia on the line. Allen, we won't talk about the [ eagles ] today, so we'll talk about something more positive, these interim results. So you're obviously an extremely experienced investigator with a lot of experience across many wet AMD programs and trials. What are your key takeaways when you look at this data set?

The data set support very strong interim safety and efficacy data for a gene therapy platform that can be performed in the office for our most frequently needed injection patients that is wet AMD. The safety issue is something to pause upon and reflect because we've seen a number of new products in the retina space that have suffered from safety issues, some of which have taken the post-approval out to essentially commercially non-viable. These safety data to date are very positive for this program and really support the idea of potentially suprachoroidal in-office gene therapy, going forward for other conditions like diabetic retinopathy. We'll need to look at those data carefully as we go forward. I think from a larger -- or zooming out to maybe 30,000 feet, retina has led in gene therapy with the first in-human gene therapy approved in 2017 for very rare diseases, Leber congenital amaurosis, FARC therapeutics. Just 3 weeks ago, we had gene therapy -- a different type of gene therapy, CRISPR gene therapy, gene modification approved for sickle cell with crisis. This biofactory gene therapy, the data set here today that Dr. Pitcher presented and that we have to date in the subretinal and also the other suprachoroidal program for diabetic retinopathy from REGENX [ have the ] support, really the viability of a gene therapy biofactory approach to common retinal diseases. I'm excited about it, and I think the colleagues were as well today here in Maui.

Thanks, Allen. So you both touched on the importance of safety in the gene therapy space historically. And of course, here in this data, we see what we were hoping to see in terms of mitigating inflammatory risk, fortunately with just a 7-week taper topical drop regimen. So, I think it would be helpful for our audience to hear your perspective when you think of one-time, in-office treatment along with this type of regimen. Is that something that you find feasible or any significant problems when you think of potential treatment for your patients? John, why don't we start with you again on this one?

Yes. I think that the topical approach with steroid drops is very palatable to patients and retina specialists. We've seen other products require much more intense suppression -- immune suppression. And in this case, the ability to achieve both mitigation of topical inflammation and potentially elimination of intraocular inflammation just with drops is potentially a game changer in the risk-benefit discussion with patients.

Allen, anything to add to that?

I would agree with Dr. Pitcher that short-course topical steroids are a completely acceptable way to control, and note that there were no recurrences of the inflammation, that these inflammatory events were mild. Yes, very acceptable. You have to -- if you contrast this with other spaces in which gene therapy is delivered, this is very much acceptable, specifically no oral steroids, no long-term topical steroids for more than several months, and no evidence of recurrent inflammation after short-course topical steroids in this -- our 314 AAVIATE presentation.

So, let's switch on over to the efficacy side of the coin. Ken, in his introductory remarks pointed out the challenge that we have translating clinical trials with repeated injection approaches where, when you then go into the real world, we see actually a continued loss of visual acuity over the years, at least in part due to the unsustainable treatment burden. And I'd like to hear both of your real world perspective. So moving away from the clinical trial setting and into your practices, what do you actually see in the real world in terms of patient adherence to the available chronic treatment regimens and how you see that translate into actual visual outcomes for your patients? Why don't we switch it up this time? Allen, if you could give us your perspective?

Yes. There are efficacy metrics that, of course, include visual acuity, how the patients are doing on the chart. There are efficacy metrics in terms of burden of treatment, how often the adult 40-year-old daughter has to take off a half day at work to come in and bring their mother in for an injection. So, certainly, gene therapy addresses burden of treatment from the standpoint of potentially less visits. In terms of vision, what I find most interesting and promising scientifically is that, if we can achieve a steady state production with this biofactory approach, with an in-office suprachoroidal injection, that maybe over time we'll see less decline in vision that we see in years 2, 3, 4, 5 in the real world and also in some of the previous injection clinical trials that were long-term follow-ups that -- for example, ranibizumab or aflibercept, maybe the pharmacokinetics of a steady state production would be permissive of maintaining stable vision over time. We're getting senses of this in long-term follow-up in the subretinal 314 program. We're getting senses of this in, for example, other platform deliveries, like a port delivery over time. Maybe we'll see less atrophy. Maybe we'll hold on to vision. That's really important, very important. Obviously, that's the key issue for patients with neovascular AMD that are being treated over time.

And John, how about your experience with your patients over time?

Yes. Still I frequently will see patients experience setbacks or vision loss due to inadequate treatment with current standard of care. And it's not always easy to avoid. Patients may travel from far distances to receive injections in all of our clinics, so they may become sick or have unreliable transportation options. And we're, I'm sure Allen would agree, always getting questions from patients about how many more injections do I need and patients being able to switch that discussion from a chronic treatable condition to a potentially curable condition. I think a one-time, in-office gene therapy option could help and obviously eliminate a lot of the obstacles we currently face in standard of care.

Great. Thanks again to both of you, John and Allen, for your expert perspectives on these interim results and how you see that translating potentially into a potential new treatment approach for treatment of your patients with wet AMD. So now we're going to turn it over to the operator to take questions from the audience. Operator?

[Operator Instructions] Our first question comes from the line of Gena Wang from Barclays.

I think I will ask maybe 2 questions, very quick ones. The first one is, dose level 3, you grouped 3 cohorts together. Any differences among cohort 4 and 5 and 6 regarding injection-free rate and the injection reduction? And the second question is more for the 2 doctors. I think on Slide 11, if we look at it, BCVA and the CRT, there was not a clear dose response. Any thoughts there regarding the both measurements?

I'll take the first question on dose level 3 and the grouping of the different cohorts. Really, the only meaningful difference was this elimination of intraocular inflammation that we saw in the cohort with topical short-course prophylaxis. Otherwise, the efficacy measures were fairly similar across the groups, and that's why we chose to combine them. I don't know if either John or Allen, do you want to comment on Gena's second question? Gena, could you repeat the second part of your question?

Second question -- Yes, sure. So, on slide 11, I think there is 3 different doses, dose level 1, 2, 3, and that was a measurement of the BCVA and the CRT. When we look at the 3 dose levels and look at the change of the CRT or BCVA, there is not a clear dose response. I wanted to ask the doctor's thoughts there.

Yes. So, John, why don't we hand that one over to you? Your perspective on what we see in terms of disease control, in terms of the stability of central retinal thickness across the 3 dose levels?

Yes, I think the point here is that the CRT and vision levels are remaining stable across the doses. I don't think there's necessarily an expected delineation there between the different dose levels. The key is that they're remaining within a range that we would expect with treatment.

Our next question comes from the line of Alec Stranahan from Bank of America.

2 quick ones from me as well. Maybe just expanding on that last line of thought, you added a third dose to the study. Given the 9A profile and now the IOI is under control at the highest dose, is there a possibility or room to add an even higher dose to the study or are you satisfied with the performance so far? And then, in terms of next steps, I know follow-up on the primaries, that's 9 months, I think safety is 12 months. So we'll get another update from the Phase II, but in terms of gating around planning a pivotal, what does that sort of look like? And who ultimately decides [ whether ] that study begins -- you or AbbVie?

As you ended your questions with the aspect of our partner, AbbVie, really, that's an important context for both parts of your question. This is a global collaboration. So, as these new cuts of data come out, we review this together and we make assessments on what additional data we want to see in follow-up in any future development decision. So given that, we're really not in a position to give any specific guidance on dose selection, for example, other than the fact that we're very pleased to have 3 different dose levels where we're seeing efficacy and seeing good safety and tolerability, as well as having learned about the ability of topical that is less invasive and in short-course prophylactic steroids to mitigate risk. So I think that puts us and AbbVie in a good position to assess how do we transition as we look at these data packages into later stage development. And I think also in terms of any specifics on future updates, same basic type of answer. Sorry, we can't give you more specifics, but that's really going to come down to further discussions with us and our global partner. Operator?

And our next question comes from the line of Ellie Merle from UBS.

Just in terms of the Phase III planning, maybe just a little bit more color on the last question asked. Would you theoretically, I guess, wait for the subretinal Phase III to read out before you would start a Phase III or pivotal and suprachoroidal and just like, how you're thinking about that? And then, I guess, what can we expect in terms of timing for when we could get some of this long-term efficacy data and just any color in terms of how that's trending beyond 6 months in terms of durability?

It's Ken. We don't have any interrelationship between the subretinal work that's going on, and we initiated those 2 pivotal trials, the first of them almost a 1.5 year ago and they continue to progress well and be on track for the guidance for the subretinal BLA that we've given in late 2025 and through early '26. So the suprachoroidal data today is our first opportunity to see this 50-patient data set at 6 months to kind of digest it with the community, bring it out there publicly. And I think, the AbbVie and the REGENX teams are going to have opportunities to now sort of interact and consider more what the longer-term data is going to look like across the course of this year. I think we've said -- since the end of last year we updated our strategic plans that coming into 2024 was going to be a data-rich year and I think the maturity of the suprachoroidal data both for wet AMD and diabetic retinopathy is something that we're excited about, to have this first data set with this -- really, I think, full cohort of dose level 3 is heading in the direction that we're encouraged about. It's January, we're going to keep focused on the work we need to do to make those decisions. But I think this is a year where we see a lot of data being able to inform important decisions for this program, but again, not related to subretinal. That's well on track for the BLA filing that we've guided to already.

And our next question comes from the line of Luca Issi from RBC.

This is Lisa on for Luca. Maybe another question on a potential pivotal. Just wondering how you are thinking about a Phase III trial design? Would the study be similar to the subretinal study comparing a single dose of gene therapy to on-label anti-VEGF or would you consider a protocol with equal injection rates? Any color there would be helpful.

Lisa, thanks for the question. Again, not a point in time today where we're giving specific guidance on any transition to pivotal or plans around pivotal. I do think that the work that went into the decisions and the trial designs for subretinal have been very consistent with what the regulatory agencies have required for assessment. And then last year, we updated further that both ATMOSPHERE and ASCENT have been strongly impacted by our worldwide partnership with AbbVie to take into consideration how ex-U.S. not just regulators, but also commercial decision makers are influenced by clinical data at pivotal phase. And I expect that those types of features and attributes will find their way into the suprachoroidal design both for wet AMD as well as for indications like diabetic retinopathy going forward. So, I think you can learn some from things that we've done and what the industry has done in terms of how to use comparators and how to assess design. But as of today, we're just excited about the 6-month update that Dr. Pitcher talked about and that Allen and the rest of the community are getting to see for the first time here.

And our next question comes from the line of Brian Skorney from Baird.