Hello, and thank you for standing by. Welcome to the Q3 2022 REGENXBIO Inc earnings call and update on ALTITUDE. At this time, all participants are in a listen-only mode. After the speaker presentation, there will be a question-and-answer session. To ask a question during the session, you will need to press star one one on your telephone. It is now my pleasure to introduce , Patrick Christmas.
Good morning, and thank you for joining us today. Earlier this morning, REGENXBIO released financial and operating results for the third quarter ended September 30th, 2022, as well as new data from our ALTITUDE trial. The press releases and data presentation are available on our website at www.regenxbio.com. Today's conference call will include forward-looking statements regarding our financial outlook and our development of RGX-314, in addition to regulatory and product development plans. These forward-looking statements are subject to risks and uncertainties that may cause actual results to differ from those forecasted and can be identified by words such as expect, plan, will, may, anticipate, believe, should, intend, and other words of similar meaning. Any such forward-looking statements are not guarantees of future performance and involve certain risks and uncertainties.
These risks are described in the Risk Factors and the Management's Discussion and Analysis sections of REGENXBIO's annual report on Form 10-K for the full year ended December 31st, 2021, and comparable Risk Factors section of REGENXBIO's quarterly reports on Form 10-Q, which are on file with the Securities and Exchange Commission and available on the SEC's website. Any information we provide on this conference call is provided only as of the date of this call, November 3rd, 2022, and we undertake no obligation to update any forward-looking statements we may make on this call on account of new information, future events, or otherwise. Please be advised that today's call is being recorded and webcast.
In addition, any unaudited or pro forma financial information that may be provided is preliminary and does not purport to project financial positions or operating results of the company. Actual results may differ materially. I would now like to turn the call over to Ken Mills, CEO of REGENXBIO. Ken?
Thank you, Patrick. Good morning, everyone. Thanks for joining us. I'm pleased to begin today's call with a recap of the recent business highlights as well as an update on our corporate goals. Vit Vasista, our Chief Financial Officer, will provide an overview of financial results for the third quarter ended September 30, 2022. We're bi-coastal today. Steve Pakola, our Chief Medical Officer, is on the West Coast, recently attending Retina Society, where he'll provide an in-depth overview of the data that was presented yesterday at the Retina Society meeting from our phase II ALTITUDE trial evaluating RGX-314 for the treatment of diabetic retinopathy or DR using suprachoroidal delivery. Towards the end of the call, we'll be joined by ALTITUDE investigator, Leila Voytovich from Duke University, and independent retina expert, Dr. Peter Kaiser from the Cleveland Clinic.
Leila and Peter will stay on with us as we open up the line for questions. At REGENXBIO, our mission is to improve lives through the curative potential of gene therapy, focused on developing therapies for diseases that have significant unmet need. We continue to be a leader in gene therapy. There are thousands of patients who have been dosed with AAV therapeutics derived from our NAV Technology Platform, and hundreds more are receiving treatment every quarter. I'm very proud of how our company has been advancing our internal pipeline, and I believe our fundamentals have never been stronger. We put into place our 5x25 strategy to progress 5 AAV therapeutics from our internal pipeline and licensed programs into pivotal stage or commercial products by 2025. I'm now going to summarize some of the program highlights and operational updates from our announcements this morning.
Our global eye care collaboration with AbbVie to develop and commercialize RGX-three one four for retina disease continues to advance and is on track for a first BLA filing in 2024. Progress in trial enrollment and emerging clinical trial data also supports excellent progress in our suprachoroidal delivery programs. At AAO, RGX-three one four subretinal delivery for the treatment of wet AMD was reported to be well-tolerated with long-term durable treatment effects now observed up to 4 years. We expect this trial, along with the two ongoing pivotal trials, ATMOSPHERE and ASCENT, to support our planned BLA submission in 2024. In October, we also announced positive interim data from the phase II AAVIATE trial of RGX-three one four for the treatment of wet AMD using suprachoroidal delivery.
These data show that RGX-314 was well-tolerated with stable BCVA and a meaningful reduction in anti-VEGF treatment burden at all dose levels out to six months. We announced the expansion of this trial to further explore the third dose level in a sixth cohort with a short course of prophylactic ocular steroids following RGX-314 administration in order to potentially prevent the observed incidence of mild to moderate intraocular inflammation. Yesterday, as I mentioned at the Retina Society meeting, new positive interim data was presented from our phase II ALTITUDE trial of RGX-314 for the treatment of DR using suprachoroidal delivery, and Steve will lead a review and discussion of these data in greater detail shortly.
We've been working diligently to prepare on the initiation of our first-in-human trial of RGX-202 for the treatment of Duchenne and continue to expect to dose the first patient in the AFFINITY DUCHENNE trial in the first half of 2023. RGX-202 is a potential one-time gene therapy for the treatment of Duchenne and being developed as a highly differentiated product designed to deliver a transgene for a novel microdystrophin. That includes the functional elements of the C-terminal domain, domains found naturally occurring in dystrophin. RGX-202 is designed to support the delivery and targeted of expression of genes throughout the skeletal and heart muscle using our NAV AAV8 vector. RGX-121 is our candidate for the treatment of mucopolysaccharidosis type II, also known as Hunter syndrome. This is currently being evaluated in an expanded pivotal phase program called CAMPSITE.
We are dosing patients in this pivotal program. Most recent positive interim data update from this study of this candidate reported that RGX-121 was well tolerated across all cohorts studied. Biomarker data from the patients in all 3 cohorts indicated encouraging dose-dependent reductions of cerebrospinal fluid GAGs following one-time administration of RGX-121. Improvements in neurodevelopmental function and caregiver-reported outcomes demonstrated CNS activity up to 2 years after RGX-121 administration. The expanded pivotal phase of this program is expected to enroll up to 10 MPS II patients using commercial scale GMP material to support a BLA filing in 2024 using the accelerated approval pathway, with the potential to enroll additional patients. This is our second active pivotal program and another opportunity for a BLA filing by 2024.
Our ongoing phase 1/2 trial of RGX-111 for the treatment of severe MPS I, or Hurler syndrome, continues with plans to enroll additional patients in cohort 2 expansion arm. Our manufacturing innovation center and GMP capacity capability remains a key differentiator for REGENXBIO and a key element of our strategy. Our in-house facility is cutting edge and allows us to move quickly from candidate selection to production of clinical grade material, which supports accelerating the early development of AAV therapeutics. Additionally, we believe our approach focuses early on product quality and process control, which lessens the need for changes during clinical development to enable efficient transition from clinical trials to commercial readiness.
I would now just like to take this time to thank our entire REGENXBIO team, all of our investigators and their support staff, and the patient communities for their commitment to the continued development of our AAV therapeutics. We certainly believe that one-time gene therapy can address a whole range of unmet needs in both chronic and rare diseases, and we remain dedicated to these patients and their families. Overall, reflecting on this quarter at this point in the year, I'm very proud of the progress we've made to advance our 5x25 strategy. With that, I will now turn the call over to Vit for a review of our third quarter results and financial guidance.
Thank you, Ken. REGENXBIO ended the quarter on September 30th, 2022, with cash equivalents and marketable securities totaling $617 million, compared to $849.3 million as of December 31st, 2021. The decrease was primarily the result of cash used to fund operating activities and capital expenditures, as well as temporary unrealized losses on marketable debt securities during the nine months ended September 30th, 2022. R&D expenses were $63.3 million for the quarter ended September 30th, 2022, compared to $47.9 million for the quarter ended September 30th, 2021. The increase was primarily attributable to personnel costs and expenses associated with clinical trials and manufacturing-related activities for our lead product candidates and was partially offset by RGX-314 development costs reimbursable by AbbVie under our eye care collaboration.
In accordance with the collaboration agreement, REGENXBIO will continue to fund certain ongoing clinical trials for RGX-314 through the end of 2022, while other RGX-314 development costs are shared with AbbVie. Beginning in 2023, AbbVie will be responsible for funding the majority of all RGX-314 development expenses. Based on our current operating plan, we expect the balance in cash equivalents, and marketable securities of $617 million as of September 30th, 2022, to fund our operations into 2025. Now, we would like to return the call over to Steve for an in-depth discussion of the recently announced ALTITUDE data.
Thank you, Vit. As Ken shared, we recently presented interim data updates for our RGX-314 trials for the treatment of wet AMD using subretinal and suprachoroidal delivery. RGX-314 is also being developed for the treatment of DR, and we're pleased to be sharing new interim data from our phase II ALTITUDE trial of RGX-314 using suprachoroidal delivery that was presented yesterday at the Retina Society meeting. Slides from that presentation can be found in the Media Presentations and Publications section on our website. Joining me this morning, we have Dr. Leila Voytovich, Associate Professor of Ophthalmology and Director of the Duke Vitreoretinal Fellowship program, and the lead investigator who presented the ALTITUDE data yesterday. We're also joined by Dr. Peter Kaiser, Director of the Center for Ocular Research and Evaluation at the Cole Eye Institute at the Cleveland Clinic.
DR is a complication of diabetes and is the leading cause of blindness in adults between the ages of 24 and 75. An estimated 27 million patients are affected by this debilitating disease worldwide. DR is a slowly progressing disease that can lead to vision-threatening complications, including diabetic macular edema, or DME, and neovascularization that can lead to blindness. Like in wet AMD, patients with DR are treated with anti-VEGF therapy, which is proven to reduce the risk of developing vision-threatening complications. However, due to the unsustainable treatment burden using anti-VEGF therapies, primarily the result of the frequent intraocular injections required, many patients with this condition put off receiving any treatment until symptoms become unavoidable. We believe a gene therapy like RGX-314 could potentially overcome this hurdle and provide an important therapy for DR patients to significantly alter their disease progression.
ALTITUDE is a multicenter, open-label, randomized, controlled dose escalation phase II trial evaluating the efficacy, safety, and tolerability of suprachoroidal delivery of RGX-314 using the SCS Microinjector in patients with a DR diagnosis of moderately severe or severe non-proliferative diabetic retinopathy, NPDR, or mild proliferative diabetic retinopathy, PDR. Patients in cohort one received RGX-314 at a dose level of 2.5E11 genome copies per eye, which we refer to as dose one, while patients in cohorts two and three received RGX-314 at an increased dose level of 5E11 GC per eye, which we refer to as dose two. Patients in cohorts one through three did not receive prophylactic corticosteroid therapy before or after RGX-314 administration. As of October 17th , 2022 RGX-314 was reported to be well-tolerated in cohorts one through three. Five serious adverse events were reported, none of which were considered drug-related.
For the total group of cohorts 1 through 3 receiving RGX-314, 50 patients in total, common ocular adverse events in the study eye through 6 months were predominantly mild and included conjunctival hemorrhage, conjunctival hyperemia, and episcleritis. In addition, 3 patients experienced intraocular inflammation, IOI, all of which were mild and resolved on topical corticosteroids. There were no meaningful differences in safety outcomes observed for patients who were MAP positive. Best-corrected visual acuity remained stable in cohorts 1 through 3 through 6 months. At 6 months, patients treated with RGX-314 demonstrated clinically meaningful improvements in disease severity versus observational control as measured by the Diabetic Retinopathy Severity Scale, or DRSS. 71% of patients in dose 2 achieved 2-step or greater improvement in DRSS score versus 10% in observational control.
Additionally, 54% of patients, representing 60% of patients in dose level one, and 51% of patients in dose level two achieved any level of DRSS improvement versus 20% in control. It's important to note that 0 out of 50 RGX-314-treated patients had at least a two-step worsening in DRSS score, while 20% of patients in the control arm experienced at least a two-step worsening. With that, I will now turn the call over to Dr. Leila Voytovich, who is sitting next to me in lovely Pasadena, where Leila, we were really excited to hear your presentation yesterday at the Retina Society meeting here. Now is really a great opportunity for us to hear your clinical perspective as lead investigator in the trial on the interim results that you presented.
Great. Thank you, Steve. It's a pleasure to be here today. I'm very excited about interim data that was presented yesterday and discussing this morning. Primarily, as Steve nicely highlighted, diabetic retinopathy is a tremendous problem, a huge public health problem globally. That relates to very busy clinics with diabetic retinopathy patients who unfortunately, because of their status and working age, cannot keep up with the treatment burden of frequent injections. That results typically in my clinic, about 90% of my patients are being watched and not treated, and often not even coming for the appointment. Clearly, there is a tremendous need for better treatment, more sustainable treatment. Having a one-time treatment in office may provide that solution. I'm excited to see the interim data results.
First of all, the efficacy looks very promising with improvements in all cohorts, including improvements in diabetic retinopathy severity scores and no disease worsening that we saw in the data results. Even more importantly, the safety results looks promising as well. The fact that we're seeing good results with minimal evidence of inflammation was encouraging to me. Overall, this translates to me for hopefully one day having a treatment option for 90% of most patients that are currently being observed who are potentially gonna have a disease affecting visual decline in the future. This option may provide a solution to their vision worsening.
Great. Thanks so much, Leila, for that perspective. As the audience can hear, we're very excited about this interim data that Leila presented and the potential of RGX-314 for patients with DR. As we continue to build upon the drug profile of RGX-314 in DR, we've made the decision to expand the ALTITUDE trial to include a higher third dose level of 1e12 GC per eye. Leila outlined that as well yesterday at the presentation. The trial is currently enrolling two new cohorts, four and five, at this third dose level.
Cohorts four and five are enrolling patients stratified by DRSS levels, with patients in cohort four having moderately severe to severe NPDR, which is DRSS levels of 47-53, and patients in cohort five have mild to moderate PDR, which is DRSS levels of 61-65. We're excited at that ability to evaluate in an expanded DRSS range. Patients in these cohorts will receive a short course of prophylactic ocular steroids following RGX-314 to evaluate the ability to prevent or reduce the incidence of the mild intraocular inflammation seen to date in a setting of no prophylactic steroids. Patients will be enrolled in these cohorts regardless of baseline AAV8 NAV status. Now we also have sitting here with us in Pasadena this morning, Dr.
Peter Kaiser, who, in addition to being an expert clinician and clinical trialist and expert across the retina space, is also a very experienced central reading center grader and expert and overseer, including assessment of diabetic retinopathy and use of the standard DRSS scale. Peter, really a perfect opportunity to really blend your expertise both clinically but also how you think of endpoints when it comes to diabetic retinopathy and use of the DRSS scale. We'd love to hear your key takeaways from this interim data updates.
Sure. Yeah. Thanks for inviting me. Leila really outlined it great, which is we have two products that are FDA approved for treatment diabetic retinopathy. The regulatory endpoint that we use is diabetic retinopathy severity scale, which really is something that we do at a reading center level. In general, at a clinical level, Leila and I won't be counting microaneurysms and looking at as closely as we do in a clinical study. It's important to understand that the DRSS was developed a long time ago, almost 35 years ago now, for the Early Treatment Diabetic Retinopathy Study. It was one of the first randomized studies done across medicine. The importance of a two-step change is that's a very significant change in the level of retinopathy.
That's why the FDA and the EMA use that for regulatory approval. However, in clinical practice, what we wanna see is overall our patients getting better. As Leila correctly pointed out, the reason we don't use the FDA-approved products both Eylea and Lucentis that often, you know, there are a few patients we do use it on, but in general we don't, is because it requires very frequent injections and these working age patients simply can't take the time off from work to get these injections or they have burnout. You know, they just don't wanna do it. Most of these patients actually have very little changes in vision, so they don't really see an improvement with these injections. But as physicians, we can see the improvement.
That really brings out the point of RGX-314. This is to me is a killer app for gene therapy. The idea of doing an in-office procedure to allow these patients to have improvement in the diabetic retinopathy severity scores, which we saw very nicely with the presentation by Leila yesterday of the ALTITUDE interim study results. This is very exciting for all of us in the retina field.
Wonderful. Thanks. Thanks so much, Peter. With that, we are ready to turn the call over for questions. Operator?
Thank you. As a reminder, to ask a question, you will need to press star one one on your telephone. Once again, to ask a question, please press star one one. Our first question comes from the line of Gena Wang with Barclays.
Hello. Thank you very much for taking our questions. This is Xu Yang for Gina. I have two questions. The first question is about the inflammation. The inflammation rate at 5e11 dose cohort seem to be pretty similar to the wet AMD at the same dose. Could you give more colors on the like the onset duration and how the inflammation was resolved? Like what steroid and how long it's used and how long does it take to resolve? I have a follow-up question on the new prophy cohort. Can you give more colors on the short course steroid? Is it similar or same as the AAVIATE for wet AMD such as administration?
Like, do you plan to use both topical and or one time subtenon injection? And what steroid will be used, and what will be the dose regimen? Thank you very much.
Thanks, Xu Yang. This is Ken . Steve, I think those questions are best directed to you and the experts there.
Great. Hi, Xu Yang. Thanks for the questions. I'll give an initial comment, and pass it over to Leila Raji to give her perspective of what she experienced within the trial, firsthand. In terms of inflammation, you're exactly right. We didn't see anything unanticipated, so we were quite pleased with the low rates of mild intraocular inflammation, and the characteristics were what we've seen previously. Nothing concerning in that we see it come on generally within two to six weeks of RGX-314, and very easily managed with a short course of topical corticosteroids. Our investigators, and we'll hear Leila Raji's perspective, you know, very happy with the profile that we're seeing that's consistent with what we've seen previously.
We also have this great opportunity to evaluate and further characterize in a setting of prophylactic steroids, where that allows the clinicians to assess how these patients do and potentially mitigate even further the risk of inflammation. We're doing that with topical ocular steroids in the expansion of the ALTITUDE study, and it'll just be a standard short course with a typical taper over weeks, which our investigators and our thought leaders are very comfortable with that type of prophylactic regimen. We have Leila here who actually dosed patients in the trial and you know is very aware of the data we saw across the trial. What was your perspective as you think of your own experience and your colleagues' experience in the trial as far as inflammation?
Yeah. Thank you, Steve. Yeah, exactly like you highlighted. Having had patients in this trial, and watching them very careful for any evidence of inflammation, I would say it was really mild. If it did present, it presented exactly 2-4 weeks after the injection, potentially up to 6. Really very rare to maybe a little more frequent in that anterior segment cell. So what does that translate? Really asymptomatic for the patient. This was something because these patients are in clinical trial setting, we're closely watching and noting. If we did see any hint of it because of our sensitivity to inflammation gene therapy trials, we were proactive in treating them. So I think the treatment, like you mentioned, is very reasonable, very effective as well in topical steroid format.
It was a short taper that was used as well for patients who did. I'll point out in this cohort is about 6% of patients overall across actually all three cohorts that had the inflammation, very manageable with topical steroids. I think what that translates to my clinical setting, I think the safety profile is promising and very manageable by a retina specialist.
Great. Thanks, Leila. Next question.
Thank you. Our next question comes from the line of Vikram Parikh with Morgan Stanley.
Good morning. This is Gospel on for Vikram. We have 2 questions. The first one is, when doctors treat patients with DR, how are they measuring progress? Are they generally looking at a two-step improvement in DRSS or for any level of improvement? Then also, you know, how do you believe the addition of a dose of prophylactic steroid will impact the commercial opportunity for RGX-314 in DR, if at all?
Thanks for.
Steve again. Right at you.
Great. Thanks, Gospel. I'm gonna direct it right away to Peter because I think both these questions, you know, fit very well for getting a clinical perspective independently of how DR patients are managed and also how to think about topical steroids.
Yeah. I'll handle the second question first. You know, when you look at any new treatment as a retina specialist, we're of a heightened sensitivity to intraocular inflammation. You know, that term is a catch-all phrase, obviously. It includes anything that we could possibly see. When I look at the results of the suprachoroidal treatment both in AMD and diabetic retinopathy of RGX-314, this is mild IOI. You know, I served on a safety review committee for Novartis, and this is not the same thing. There's no retinal artery occlusions, retinal vein occlusion, retinal vasculitis. This is very mild intraocular inflammation that's treated with a short course of steroids. To me that's not a big deal, so I'm not concerned about that.
Certainly, we have to see more patients, but so far none of the data concerns me in any way. In terms of the first part of your question, DRSS. You know, we do that at a reading center level. This requires really carefully counting microaneurysms, venous beading, et cetera. In clinical practice, the average Joe retina specialist is absolutely not going to do that. What we are going to do is look at these patients over time to make sure that they're improving. In other words, if they have early neovascularization, so like level 61, which was enrolled in this clinical study, we're going to be watching that neovascularization very closely with any of our treatments for that matter, to make sure that that area is resolving.
In other words, we would expect with our treatment that that neovascularization would disappear, because that neovascularization is what leads to future vision problems, tractional detachments, vitreous hemorrhage, and that's what causes eventually blindness untreated. That's what we are most worried about. Over time, we would watch to make sure they disappear, but we also like to see the hemorrhages and the microaneurysms disappear also. This is something we can very easily do with a clinical exam. Most retina specialists are not doing a formal DRSS evaluation. We're just looking at the patient through a dilated fundus exam. Got it. Thank you very much.
Thank you. Our next question comes from the line of Alec Stranahan with Bank of America.
Hey, guys. Thanks for taking our questions. Just a couple from us, also on DR. First, maybe you could talk about the rationale for adding the higher dose level in ALTITUDE. Is there a certain bar on DRSS or some other metrics that you'd ideally like to hit that you're not already? Just trying to understand how you're thinking of the data thus far, given it looks like there was actually a step down in DRSS improvement from dose 1 to dose 2, but maybe there's a bullet of 1-step improvers in cohort 3. Secondly, could you talk about the observational control in the study? Is this an appropriate comparator arm through your discussions with the FDA?
I guess looking at a pivotal study, do you think you would need to run a head-to-head similar to what you're doing in the wet AMD program? Thanks.
Thanks, Alex. In terms of rationale for the higher dose, these are both the AAVIATE study and ALTITUDE. These are the first two studies ever evaluating suprachoroidal delivery of gene therapy for these indications. This is really an exciting time for the field and for us to really characterize RGX-314 via this route of administration. We actually have the interim data that we presented with dose level three in the wet AMD setting from the AAVIATE study. We in effect have a head start of evaluating this. It made perfect sense for us and our strategic partner, AbbVie, to continue to evaluate in this study. Regarding dose level one and dose level two, as Peter mentioned, there are various cuts and ways to look at change in DRSS.
The reality is, when we look at the totality of this data, we see what we want to see in terms of both dose level one and dose level two. That aspect as far as what we would need to do in a pivotal study, there we are very confident in an observation control for the reasons that Leila and Peter both nicely elucidated that even though we know available repeated injections work, quote-unquote, in terms of improving DRSS and improving DR and preventing vision-threatening complications, those treatments are simply not used only in a rare proportion of patients as Leila mentioned. Standard of care is really still watchful waiting. An observation control is ideal for this setting and one of the nice things about DR development.
It's nice that we have the concurrent control in this trial where we see what you'd expect to see. I think either, you know, Leila or Peter, it'd be great when you look at our observation control and you think of precedence controls in the literature and your own clinical experience, what do you expect to see if you don't treat patients?
Thank you, Steve. Yeah, no, exactly what you highlighted. I would expect to see progression over time to vision worsening and complications from diabetic retinopathy. I similarly will echo, I think observational arm is very acceptable because that is the real-world setting currently. We are observing these patients not treating them with frequent injections. From my personal opinion and really experience in the clinical across the board, it's quite acceptable.
Yeah, I fully agree. The current clinical standard from a regulatory standpoint is not to do a head-to-head study against intravitreal anti-VEGF injections. That would not be required. A sham control in this disease is not only regulatory reasonable, it's also a very doable study.
You know, my patients, the opposite is if you put an anti-VEGF as a control, it'd be very hard for me to get a patient into the study. So it's the opposite of what you would think. From a regulatory standpoint, absolutely, totally, fine to do a sham control. In terms of numbers, you know, I think this, the beauty of this data set is that there is a control group. So you can kind of see what happens over time and what's happening to this control group at a six-month interim data is sort of what we'd expect. About 20% or so are having a pretty significant worsening. A few patients get better.
If you look at the control groups, say VIM and VISTA, RIDE, et cetera, some of PANORAMA, some of these other studies that have been done, it's about 10%-15% will actually improve a little bit. Largely, that's not due to the fact that the disease is getting better. In general, what that is that the patient in that study suddenly realized, oh, wait a minute, I actually need to do better control my sugars, better control my blood pressure because I'm in this study. And that's what leads to that improvement. It's nothing to do with like. In general, as Lena said, these patients are gonna go downhill. They don't improve. If you do improve your sugars and blood pressure, that will improve things.
We've seen that in like the UKPDS and the DCCT studies in the past.
Thank you.
Thank you. Our next question comes from the line of Ellie Merle with UBS.
Hi, this is Sarah in for Ellie. Thanks so much for taking our question. I guess looking at the change in DRSS score that you see at month 6, differences across cohorts between sort of no worsening or no change on a greater than 2-step or even 1-step improvement. I guess, do you look at this as an effect of the neutralizing antibody status, and thoughts about that moving forward into a potential phase III or labeling? And then I guess a second question is any detail or color that you can provide on the 5 SAEs that occurred during treatment would be great. Thanks so much.
Great. Thanks, Sarah. On your first question about the different cohorts and the different dose levels and the NAB status. Very similar to what we see in the AAVIATE study, we've not seen an impact as we look at this data. Of course, with 15-20 patients per cohort, you're gonna have some variability that you would anticipate. Also thinking of baseline DRSS, how severe you are at baseline is a variable that can impact whether you can improve two steps or not. I think this actually would be a good question. I'll turn it over to Peter to talk about that nuance of grading and how to think of data based on baseline characteristics.
Certainly if you take that into account, we find, and again, looking at the totality of the data that in each of the dose levels, in each of the cohorts, that patients are moving in the right direction, unlike the control arm, if you really take into account all the variables of not worsening by a lot like a couple of the control subjects and having improvements on average in the others. Again, we have to not only look at these results, but also our AAV study to really assess how do NABs matter, or not. That's why we chose in the expansion to enroll patients independent of their NAB status. We'll still measure it, and we'll still be able to assess that to see if we continue to see no impact there.
I think before I go to the next question. Yeah, I think Peter, I think it's a nice question to really get your sense when you tease into the data, how do you look across cohorts based on the baseline characteristics, for example, for these patients?
Yeah, I think you know, whenever you look at interim data, especially in phase II, with relatively small numbers of patients, you don't want to read too much into it. You want to look at the totality of the data. To me, if you look at all the cohorts, you know, they're trending in the right direction. There's right shifts in every single cohort, whereas in the control group, you don't see a shift at all, which is what you expect, and maybe even a slight left shift, which eventually untreated you'd expect to occur over time. If you look at, say, cohort 1 versus 2 and 3, there's actually a very large imbalance at baseline with the DRSS scores. It's a very important imbalance.
In cohort one, there's more patients in an early PDR, so level 61. Level 61 is a really minimal amount of neovascularization at the disc. To move that 2 steps forward is actually very easy with just a little bit of anti-VEGF. Like any anti-VEGF given to a patient with mild NVD, that NVD is gonna disappear, and they quickly go to 57 and then drop even further thereafter. Whereas you take somebody who's, say, severe NPDR and try to improve them 2 steps, that's a much bigger change in terms of what needs to be done to the eye. You know, if you have a lot of PDRs, early PDRs, it's going to be easier to show a 2-step change. That's not what we care about.
We care about the overall population of patients. To me, that's what I said at the beginning, that the right shift of all these patients is what's more exciting than really looking, you know, granularly at a few patients who just kinda went one way or the other way, right at six-month time point.
Great. Sarah, your other question on SAEs. None of the 5 SAEs were considered drug-related, and they're really the types of things that happen to patients, diabetic patients, who on average are older, not quite as old as the wet AMD patients. Just to give you an example, broken femur, other unrelated aspects. In fact, the only ocular SAE happened in the fellow eye for the patient who had a worsening vitreous hemorrhage. Overall very clean from a safety standpoint.
Great. Thanks so much.
Thank you. Our next question comes from the line of Luca with RBC Capital Markets.
Oh, great. Thanks for taking our questions. This is Lisa for Luca. Just two questions from us. Wondering if you can elaborate more on the decision to include prophylactic steroids. Was this due to the diabetic retinopathy data alone or the totality of the data between the diabetic retinopathy and wet AMD program? You know, on the baseline characteristics, I noticed that the cohort two and three patients had no prior anti-VEGF injections, but the cohort one patients did, and they appeared to respond a little bit better. So just wondering going forward for the high-dose cohort, will you enroll patients who are anti-VEGF experienced versus anti-VEGF naive? Thanks.
Thanks, Lisa. To elaborate more on the decision to expand. You know, again, we take advantage of all the data we have, so that's one of the nice aspects of having both a wet AMD AAV8 study ongoing as well as this ALTITUDE study in DR patients. It really gives us a chance to look at safety and tolerability and also biologic effect for these VEGF-driven retinopathies. We're very pleased with our partner at AbbVie. You know, we look in concert at these interim data, and I think it was a very natural decision to go up on dose to dose level 3, as we did with the same exact dose in AAV8. The second question, Lisa, on previous treatment.
Yes, as you mentioned, there were some patients in one of the cohorts who had previous treatment. What we do in these types of studies is we make sure there's a certain washout window. Even if that patient is not, quote-unquote, treatment naive, they at least have not had an anti-VEGF injection in at least six months to minimize the risk of a confounding factor there. There were actually some interesting presentations yesterday getting into from other programs thinking about treatment naive versus not. We'll follow with that same approach going forward. We haven't amended that part of the protocol where a patient can have had prior anti-VEGF, but not within a recent timeframe.
Great. Thanks for taking our question.
Thank you. Our next question comes from the line of Andreas with Wedbush .
Good morning, and thanks for taking our question. 2 for us. On the bottom of slide 9, it says that a couple of patients received anti-VEGF therapy here. Could you tell us how we determine if patients receive standard of care and what's the criteria? I have a follow-up.
Sure. In patients with this disease, of course, we look for complications and the investigators look for complications. At the end of the day, the investigator and we, of course, the sponsor agree if it's indicated to treat a patient that they should proceed with treatment. It certainly with the longer we follow these patients, that's one of the key potential benefits of a sustained anti-VEGF treatment is the ability to prevent patients from developing vision-threatening complications. We have the one patient in the control group who did need treatment that we elaborate on in the footnote, who even with treatment, wound up with four-step worsening at the end.
We had a lone patient in the 50 RGX-314 treated eyes that had a single anti-VEGF injection early in the course, and you see how that patient did. If you look at the totality of this data, that also directionally goes in the same shift in terms of outcomes that Peter discussed in terms of how we look also at the imaging basis of how severe the diabetic retinopathy is. Leila, as you know, presented this data, you have a perspective on thinking of retreatment and the realities of that aspect when you think of this kind of patient population that goes up to 61 and then 65, where we're including those patients because they're at very high risk of advancing.
How do you think of that in terms of the risk of going to DME and high-risk PDR and needing treatment?
Yeah. Steve, as you pointed out, you know, other historic diabetic retinopathy trials have not typically included mild PDR or moderate PDR as you are doing that in this trial. With that inclusion, while there may be, you know, significant gains to have, there's also risk of progression, especially early on in the treatment protocol. As you point out, the one patient that did receive anti-VEGF injection was really quite soon after enrollment. One wonders whether there was any response to the treatment that early in enrollment period. It was also higher diabetic retinopathy severity towards the mild PDR patients. We are right there set up for unfortunately already progressing to complication. I think that could be very well explained by that.
Okay, great. You might have touched on this a bit in the previous questions here. Just so thinking about or observing the decrease in greater than two-step improvement observed from cohort 1 to cohort 2 and 3, how are you thinking about or what are your expectations for the higher dose? Thank you.
Andreas, we'll have to see, of course. That's why we do the trial. We are encouraged that with dose level 1 and dose level 2 we're seeing what we wanna see. Now to have this opportunity to look at a higher dose level. As Leila mentioned, we're also expanding to include not only the mild PDR, but also the moderate PDR. We're stratifying based on that. We're gonna have a lot more patients and a lot more data to really assess dose response here, as well as how we can assess it in wet AMD and really learn from both.
Okay, thank you.
Thank you. As a reminder, to ask a question, please press star one one. Our next question comes from the line of Daniil Gataulin with Chardan.
Yes, good morning. Thank you for taking the question. I have one on potential improvement from 6 to 12 months. You previously shared the data on improvement from 3 to 6 months and compared that to the standard of care, Lucentis and Ozurdex. Wanted to see what if you can, you know, how that continues to progress beyond 6 months, and what would be your expectations for 2 and 4.
In the existing cohorts and then going forward, we care about these time points that we've presented to date. We certainly look forward to compiling and cleaning and being able to report in the future on longer term follow-up time points for these cohorts, including the one-year time point. As far as expectations, I think one aspect is for illustrative reasons, one can think of what's been done before, how repeat injections with existing therapies impacts diabetic retinopathy severity. The realities of as treatment frequency decreases and patients fall off use, that the diabetic retinopathy severity returns.
I think as our guests have highlighted, we know without treatment, which would be the observation control in a future study, that patients in general do not get better, and it's just that small percentage of patients that get better due to other factors that Peter highlighted. It really puts us in a good position in terms of a regulatory standpoint if we think of bigger studies that are powered and take out the risk of imbalances in terms of hitting a regulatory bar, while also hitting what ultimately matters to the investigators and the patients. Which is shifting the severity to the right into the favorable direction, and keeping patients from getting worse and developing the blinding complications that Peter highlighted.
Got it. Thank you very much.
Thank you. I'm showing no further questions. With that, I'll hand the call back over to CEO Ken Mills, for any closing remarks.
Thanks, operator. I appreciate that. Steve, thanks for walking us through that overview. Really grateful to Drs Voytovich and Kaiser for both their time early this morning, their perspectives on treatment paradigms in DR and perspectives and weighing in on the new interim data from the ALTITUDE trial. Just wanna reiterate that REGENXBIO continues to perform at a very high level. We have an amazing team, one that's dedicated to expandin
We have a foundation of capital over $600 million to fund our mission and operations into 2025 and through multiple filings and other anticipated data milestones. Truly believe we have a clear and definable path to achieve our 5x'25 vision to advance five AAV therapeutics from our internal pipeline and licensed programs into pivotal stage or commercial products by 2025. We look forward to keeping you all updated on our progress as we finish the year, begin to look ahead at 2023. Again, thanks very much to our guests and the entire team, and have a great rest of the day.
Ladies and gentlemen, this concludes today's conference call. Thank you for participating, and you may now disconnect.