REGENXBIO Inc. Q1 FY2023 Earnings Call

Good day, and thank you for joining us. Welcome to the REGENXBIO Inc. First Quarter 2023 Conference Call. Please note that this conference is being recorded. I will now turn the call over to your speaker today, Patrick Christmas, Executive Vice President and Chief Legal Officer. Please proceed.

Good afternoon, and thank you for joining us today. Earlier this afternoon, REGENXBIO released financial and operating results for the first quarter ended March 31, 2023. The press release 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 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 31, 2022, and the 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, May 3, 2023. 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 afternoon, again, everyone. Thanks for joining us. I'm pleased to begin today's call by recapping our recent business highlights as well as providing an update on our corporate goals. Dr. Steve Pakola, our Chief Medical Officer, will then provide an update on our clinical programs, and Vit Vasista, our Chief Financial Officer, will provide an overview of financial results for the first quarter ended March 31, 2023. At the end of the call, we will open up the line for questions. At REGENXBIO, our mission is to improve lives through the curative potential of gene therapy, and we're focused on developing therapies for diseases that have significant unmet need. We continue to be a leader in gene therapy with thousands of patients who have been dosed with AAV therapeutics derived from our NAV Technology Platform. There has been meaningful progress in the gene therapy industry lately, including a growing understanding of gene therapy pricing models and the FDA validation of surrogate markers as viable clinical endpoints. REGENXBIO continues to work closely with our regulatory partners to help advance and accelerate the development of gene therapies, particularly for rare diseases. Today, I'm pleased to discuss how REGENXBIO remains a leader in gene therapy as we share how our 5x'25 strategy is on track for advancing five AAV therapeutics from our internal pipeline and licensed programs into pivotal stage or commercial products by 2025. Our end-to-end capabilities continue to set us apart as a leader, with our in-house manufacturing innovation center running scalable, commercial-ready batches of our AAV therapeutics and our research and early development experts continuing to advance what's possible in gene therapy. In fact, this week, we announced a summary of around 15 presentations at the upcoming ASGCT conference, which reflect leadership in areas such as engineering novel NAV capsids for better targeting of AAV therapeutics to clinically relevant tissues and organs, enhancing AAV therapeutics tissue and cell type specificity and expression, including optimizing enhancer and promoter combinations, optimizing devices and routes of delivery for AAV therapeutics and other proof-of-concept research that informs next steps in our pipeline strategy. Today, we also announced significant updates and progress in our global eye care collaboration with AbbVie, including the transfer of INDs for all ongoing clinical trials to AbbVie as originally outlined in the collaboration agreement and the global expansion of pivotal trials ATMOSPHERE and ASCENT for the treatment of wet age-related macular degeneration or wet AMD using subretinal delivery. Our investigational one-time gene therapy formerly known as RGX-314 has been renamed ABBV-RGX-314. From now on, I will refer to it as 314. The new global site plans and expanded enrollment targets for ATMOSPHERE and ASCENT involve updates to our U.S. plans and new guidance for global regulatory milestones. These trials are now expected to support regulatory submissions with the FDA and the EMA in late 2025 through the first half of 2026. Steve will share additional clinical details, but first, I want to frame our view of how today's update of the global expansion further optimizes the value and enhances the robustness of the 314 program. I want to make clear where we are today, what is our clinical experience with 314 and how we view the global commercial opportunity for RGX-314. In major retinal vascular diseases such as wet AMD, the current standard of care, anti-VEGF treatments, require patients to receive injections in every eye every 4 to 12 weeks for the duration of the disease. First-generation anti-VEGF treatments are not effective enough, and emerging second-generation anti-VEGF treatments are making an impact for some patients with longer incremental acting mechanisms. However, real-world evidence consistently shows that vision improvements lag behind the controlled clinical trial evidence. Patients cannot be treated with the required frequency of both the first- and second-generation anti-VEGF treatments, and they do not control the disease well enough between doses. Together with AbbVie, we're developing 314 to be the first one-time option in major retinal vascular diseases to address the significant unmet need in the treatment of wet AMD and diseases like diabetic retinopathy and other chronic retinal conditions. A main goal in partnering our gene therapy leadership with AbbVie's global infrastructure and leadership in eye care was to expand beyond our U.S. footprint to bring 314 to patients worldwide. We believe we are in a great position to optimize the opportunity for creating value with 314 for patients worldwide. We have the largest global clinical program for the one-time treatment option in major retinal vascular diseases. This involves seven ongoing clinical trials, including two pivotal trials, global; three Phase II trials; and we're studying two delivery devices for subretinal and suprachoroidal delivery in two different lead indications, wet AMD and diabetic retinopathy, with opportunities to expand further into several other adjacent retinal diseases. Additionally, as I mentioned before, REGENXBIO's manufacturing innovation center, which is here in Maryland, is a fully operational, state-of-the-art GMP gene therapy manufacturing facility designed to meet global clinical and commercial regulatory standards. Our NAVXpress platform process is already being used in the pivotal trials for 314, and the REGENX manufacturing innovation center is on track to produce U.S. commercial supply operating at 500-liter level with bioreactors to support commercialization and with an option to expand up to 2,000 liters as needed. In 2023, we plan to use the manufacturing innovation center to produce that commercial-scale GMP material for the entire 314 clinical program as well as performance qualification lots to support planned regulatory filings. To summarize our clinical experience, in total, more than 600 patients have been dosed in the 314 program, representing over 400 patient years of exposure across seven trials. The totality of the clinical evidence shared to date shows the treatment of RGX-314 using both subretinal and suprachoroidal delivery methods is generally well tolerated. Patients are generally responding to the one-time treatment of 314. Long-term follow-up in our subretinal studies has shown durability over four years with stable to improved BCVA and a meaningful reduction in anti-VEGF burden with the majority of patients being injection-free. Now real-world evidence shows that patients with wet AMD are severely undertreated due to the unsustainable burden of these frequent injections. We believe the profile of 314 as a potential one-time treatment addresses this high unmet need, and the majority of patients currently on a higher level of standard care could transition to a one-time gene therapy. Together with AbbVie, we're developing 314 to be the first one-time therapeutic option in major retinal vascular diseases to address significant unmet need for patients. This is a worldwide opportunity with a potential to reach over 30 million patients with high unmet need and what is already calculated to be over a $14 billion global anti-VEGF market. Additionally, today, the utilization of anti-VEGF to treat diseases like early diabetic retinopathy is low, and the treatment burden is high. Less than 1% of patients with early disease are treated with intravitreal injections. We believe that there is a potential for 314 as a single in-office injection to become a new standard of care for early diabetic retinopathy treatment to prevent vision loss. An estimated 6 million patients have early diabetic retinopathy in the U.S. alone, and diabetic retinopathy is expected to become a potential $15 billion global market in the next decade supported by the right treatment profile, such as a one-time treatment. So with that, I'm going to turn the call over to Steve so he can get into greater depth on our 314 clinical progress and also discuss our rare disease pipeline and progress updates. Steve?

Thanks, Ken. I'll begin with an update on 314. 314 uses the NAV AAV8 vector to deliver a gene encoding a therapeutic antibody fragment to inhibit vascular endothelial growth factor, or VEGF. Building on what Ken shared, I want to share more about 314 for the treatment of wet AMD using subretinal delivery and the program we are running to support new global registration plans. REGENXBIO and AbbVie have expanded enrollment in the ongoing ATMOSPHERE and ASCENT trials, the two pivotal clinical trials evaluating 314 in patients with wet AMD using subretinal delivery to include patients in the U.S., Europe, Japan and Israel. ATMOSPHERE and ASCENT will enroll approximately 540 and 660 patients, respectively. This action will increase the power of primary and secondary endpoints to enable these global regulatory submissions and labeling options. Additionally, we shared interim data updates in February from the Phase II BRIDGING study. This study is designed to evaluate the same dose levels being used in the two pivotal trials. In this trial, material from our proprietary NAVXpress platform manufacturing process was well tolerated with patients demonstrating stable to improved BCVA and central retinal thickness, along with meaningful reductions in anti-VEGF burden. The majority of patients were injection-free following treatment with 314. Lastly, we also announced today that a fellow eye treatment study has been initiated as part of the pivotal program using subretinal delivery. This study will evaluate the safety, efficacy and immunogenicity of subretinal 314 administration in the fellow eye of patients from ATMOSPHERE and ASCENT who have bilateral disease and previously received a subretinal injection of 314. Data from patients enrolled in this study are expected to further support global regulatory submission plans. We also continue to advance two additional 314 programs for the treatment of wet AMD and diabetic retinopathy using in-office suprachoroidal delivery. We completed enrollment of cohort 6 in the Phase II AVA trial, a randomized dose escalation study evaluating 314 in subjects with wet AMD. Cohort 6 is evaluating the third dose level with short-course prophylactic ocular steroids following 314 administration to assess the ability to prevent or reduce the occurrence of mild to moderate intraocular inflammation seen in previous cohorts. Patients were enrolled in cohort 6 regardless of neutralizing antibody or NAB status based on results from prior cohorts showing similar safety and efficacy regardless of baseline NAB status. We continue to expect to report additional interim trial data from this trial, including initial data from cohort 6, in the second half of 2023. We also completed enrollment in cohorts 4 and 5 of the Phase II ALTITUDE trial, our multicenter, open-label, randomized, controlled dose escalation trial evaluating suprachoroidal delivery of 314 in patients with diabetic retinopathy. Cohorts 4 and 5 are evaluating 314 at the higher third dose level with patients stratified by diabetic retinopathy severity scale or DRSS levels, and all receiving short-course prophylactic ocular steroids following 314 administration to potentially prevent the observed incidence of mild intraocular inflammation. Therefore, we also continue to expect to report additional interim trial data from these cohorts in the second half of 2023. Shifting to our rare disease portfolio. RGX-202 is our potential one-time gene therapy for the treatment of Duchenne muscular dystrophy 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 or CT domain found in naturally occurring dystrophin. In preclinical studies, the presence of the CT domain has been shown to recruit several key proteins to the muscle cell membrane, leading to improved muscle resistance to contraction-induced muscle damage in dystrophic mice models. Additional design features, including codon optimization and reduced CPG content, have the potential to improve gene expression, increase translational efficiency, and reduce immunogenicity. RGX-202 is designed to support the delivery and targeted gene expression throughout skeletal and heart muscle using our NAV AAV8 vector and a well-characterized muscle-specific promoter. We were pleased to participate in the CureDuchenne Futures conference and look forward to additional opportunities to engage with the Duchenne community throughout the year. We are actively recruiting patients in our Phase I/II AFFINITY DUCHENNE trial using commercial-scale cGMP material from our manufacturing innovation center. Data collected in the trial include safety and tolerability, as well as microdystrophin protein expression levels by three months and muscle strength and functional measures and muscle MRI at later time points. We expect to report initial data from this trial in the second half of 2023. Continuing on to our two programs for mucopolysaccharidosis, RGX-121 for MPS II and RGX-111 for MPS I. RGX-121 is an investigational one-time AAV therapeutic for the treatment of MPS II, also known as Hunter syndrome, using the NAV AAV9 vector to deliver the gene that encodes the I2S enzyme being evaluated in the ongoing Phase I/II/III CAMPSIITE trial. We recently announced additional interim data from the Phase I/II part of the trial during the 2023 WORLDSymposium in February that demonstrated RGX-121 continues to be well tolerated across 15 patients. Patients receiving the pivotal program dose level continued to demonstrate the largest reductions in CSF GAGs, including Heparin Sulfate and D2S6, which approached normal levels at 48 weeks. In addition, improvements in neurodevelopmental and daily activity skill acquisition were observed up to three years after RGX-121 administration. We expect to complete enrollment in the first half of 2023 to support a BLA filing in 2024 using the accelerated approval pathway. Moving to RGX-111, an investigational one-time AAV therapeutic for the treatment of severe MPS I using the NAV AAV9 vector to deliver the IDUA gene. We have completed enrollment of the Phase I/II trial of RGX-111 for the treatment of MPS I and plan to use commercial-scale cGMP material being manufactured at our manufacturing innovation center using the NAVXpress platform process to support its continued development. We recently announced additional positive interim data from the Phase I/II trial at the 2023 WORLDSymposium in February, demonstrating that RGX-111 was well tolerated in eight patients. Biomarker and neurodevelopmental assessments indicated an encouraging CNS profile in patients dosed with RGX-111. We expect to share additional updates on plans for this program in the second half of 2023. Following these two programs, we are also developing RGX-181 to treat neurodegenerative manifestations and RGX-381 to treat ocular manifestations of CLN2 or Batten disease. We expect to initiate dosing in the first-in-human study of RGX-381 in the first half of 2023. To conclude, we have made significant progress with data updates and trial progression across all programs in our pipeline as we continue working toward our goal of 5x'25. At this time, I'd like to thank the patients, families, clinicians, and patient advocacy representatives who are involved in and support these trials, without whom these advances in one-time gene therapy development would simply not be possible. And with that, I turn the call over to Vit to review our financial guidance. Vit?

Thank you, Dr. Pakola. REGENXBIO ended the quarter on March 31, 2023, with cash, cash equivalents, and marketable securities totaling $474 million compared to $565 million as of December 31, 2022. The decrease was primarily driven by cash used to fund operating activities during the first quarter of 2023. R&D expenses were $59 million for the first quarter of 2023 compared to $56 million for the first quarter of 2022. The increase was primarily attributable to personnel costs as a result of increased headcount and laboratory and facilities costs driven primarily by the activation of the REGENXBIO manufacturing innovation center in mid-2022. We expect the balance in cash, cash equivalents, and marketable securities of $474 million as of March 31, 2023, to fund our operations into 2025. This cash runway guidance is based on the company's current operational plans and excludes the impact of any payments that may be received from AbbVie upon the achievement of development or commercial milestones under our 314 collaboration. With that, I will turn the call back to Ken to provide final thoughts.

Thanks, Vit. We continue to perform at a high level as we execute our mission of improving lives through the curative potential of gene therapy. The updates from our Eye Care collaboration with AbbVie today represent a serious and continued commitment to the innovation involved in addressing unmet needs and bringing a paradigm shift to the treatment of major retinal diseases worldwide. We're focused on optimizing the value of the opportunity for 314 by expanding its global reach and supporting the profile of this potential one-time treatment. Steve did a great job of summarizing a lot of the progress we've made here in the first quarter. Looking ahead to the remainder of the year, we anticipate a number of key milestones that will continue to highlight the potential of our one-time AAV gene therapies. The interim updates expected in the second half of the year for AAVIATE and ALTITUDE suprachoroidal trials, the initial data from the AFFINITY DUCHENNE trial in the second half of the year, completing enrollment in the first half of the year in the CAMPSIITE trial for 121 to support the BLA submission in 2024 using the accelerated approval pathway, and sharing additional updates on program plans for 111, 181, and 381 for Hurler syndrome and Batten disease are all important upcoming milestones. We have a lot of important value-driving catalysts ahead of us this year with a balance sheet to fund our mission and operations into 2025. With a focused and high-performing team, strong collaborators and the trust of clinical and patient community partners, I believe we have a clear and definable path to achieve our 5x'25 vision and continue to lead what's possible for AAV therapeutics. We look forward to providing you updates as we continue on this path throughout the upcoming year. With that, operator, I think we are ready to transition to Q&A.

First question comes from Gena Wang with Barclays.

I have two parts of the question. First one is regarding the ATMOSPHERE and ASCENT upsizing by AbbVie. So wondering, can you remind us the assumption for the three cohort study? And with increased power, what secondary endpoint will be important for regulatory submission? And related question for the manufacturing process from the in-house NAVXpress platform. What percentage of patients need to be dosed in order to clear regulatory requirements? My second question is regarding the DMD, second half this year to update. I assume the safety also will be a very important update there. What kind of a safety profile will warrant the removal of the prophylactic SOLIRIS treatment?

Thanks, Gena. I'm going to let Steve address the first question and circle back on the last two.

Gena, thanks for the questions. Taking the first part of your first question, basically, the powering concepts for the two pivotal studies have always been reasonably standard powered for the primary endpoint to have at least 90% power. As we've informed in the press release, now that we have a global partner with AbbVie, we can think beyond the U.S. and really think of the tremendous opportunity we have to globally develop to reach more patients. With more patients, we can increase power for also the secondary endpoints. That can be particularly important when thinking of labeling and associated health technology assessment negotiations that, for example, occur in Europe. So for that reason, we're very excited about increasing the sample size. As for which secondary endpoints we achieve greater power for, of course, with more patients, there's greater power across the board. But some of the ones that are potentially particularly interesting are the value drivers of decreased treatment burden. So with more patients, we can look across all these different cuts of treatment burden, for example, what's the supplemental injection rate of patients after treatment with RGX-314, what's the reduction in that treatment burden, what proportion of patients required no injections, what proportion of patients require less than certain other thresholds. And that's just to name a few. We're well excited at the opportunities that we have for greater power across the board for these to help us in our planning.

I don't know, Gena, that we have a cutoff for the percentage of patients that are required across the different global regulatory agencies. I think there's generally a perspective, and we've already started to adopt the use of the process in the pivotal trials as well as the other global expansion trials like the fellow eye work. We've also used bioreactor process almost from the beginning in AAVIATE and ALTITUDE. So I think we feel like we're in a great place. Really, what we're focused on right now with respect to manufacturing work is the qualification lots that will support commercial inventory, which will begin in 2023. And with respect to RGX-202, we are early in the process of evaluating safety and tolerability. We said we'll have our first updates in the second half of this year. We'll be relying on internal expertise and experiences, as well as the guidance from specialists in the field for the implementation of the immunosuppression protocol, including eculizumab. This was a very important multi-stakeholder process that we went through to begin. We'll continue to inform our forward-looking decisions on the same basis.

Next question comes from Dane Leone with Raymond James.

Congrats on the progress. Could you just maybe clarify for everyone whether there was actually an alteration in the agreement with AbbVie? I think some of us had thought that there would be a transfer of the regulatory responsibilities as the cost shift occurred in '23. So just trying to understand the nuance of what may have changed in the agreement. And then secondly, could you just opine a little on some of the poster presentations that you have coming up at ASGCT? Curious to know how serious we should take the GA program that's being presented there. If you have a view on terms of bringing that into the clinic, what the timeline might be for that.

Thanks, Dane. I appreciate the question. The message on the agreement side is landing the way we intended. We've said since early 2023 that under our original collaboration, AbbVie has transitioned to taking on the majority of program costs, which we originally expected for the IND transfer to occur, overlapping with today's announcement of the global expansion for ATMOSPHERE and ASCENT. This is not something new with respect to the original collaboration understanding. These are all programmatic elements being implemented now that we're over a year into the collaboration. With respect to the ASGCT presentations and posters, we're excited to share a lot about the research that goes on within REGENXBIO across multiple different therapeutic areas. We have a strong interest in indications that extend into areas we already work, including retina. We have a strong research engine led by Olivier and his team, and we will continue to look for high-value indications to add to our pipeline. This is an opportunity for us to showcase some of the basic research that's going on but certainly not any specific guidance about any new INDs that we are announcing today.

If I could just add one follow-up to that. I was excited to see the addition of the bilateral cohort being run. Is that endeavor that would actually need a separate study? Or is the cohort that you're going to be exploring fellow eye treatment in could suffice for actually having a label at the end of ATMOSPHERE and the pivotal program to allow bilateral treatment?

Dane, yes, this fellow eye protocol allows patients who have been treated in either ATMOSPHERE or ASCENT to have their fellow eye treated with RGX-314. This was part of our end-of-Phase II meeting discussions with the FDA where this was certainly part of the package that we have some exposures in fellow eye to allow dual eye treatment.

Next question comes from Gospel Enyindah-Asonye with Morgan Stanley.

This is Gospel on for Vikram. So we have two questions. The first one is how does the decision to expand enrollment in ATMOSPHERE and ASCENT impact your thinking on the registration pathway and all pivotal studies for the suprachoroidal delivery of wet AMD? And then the second one is for the RGX data expected in the second half of this year. Would you expect to release this data in a top-line release? Or is there a medical conference or venue that would be suitable for it?

Yes. Thanks, Gospel. I can hit these, and then Steve has more to offer. I don't see a direct impact with respect to the regulatory path for the registration plans for subretinal. We are very advanced with that and continue to prepare for qualifying lots for commercial manufacturing. I view us as hurdling towards important regulatory approval milestones that we've guided on both in the U.S. and outside for the subretinal approach. For suprachoroidal delivery, we're in dose-ranging mode in Phase II. There's no direct relationship between subretinal approvals and the progress of suprachoroidal delivery. We continue to see that they are tethered by the shared pharmacology.

Regarding AAVIATE and ALTITUDE, those decisions are made closer to the data review point in time. Our practice has been to present updates at medical conferences, and AbbVie typically shares that view when we collaborate on these topics.

On the RGX-202 side, we haven't provided an update on the patient enrollment today.

Next question comes from Alec Stranahan with Bank of America.

Just two from us. Appreciate all the color on 314 and the updates on the AbbVie partnership. Any additional details on the thought process that would go into moving 314 into pivotal studies for suprachoroidal delivery or in DR? Is this now under AbbVie's full discretion? And secondly, on DMD, given that you're preexisting patients into AFFINITY BEYOND, is there an expectation that a subset of DMD patients could have preexisting AAV8 antibodies that could lower efficacy of RGX-202? A refresh on any mitigation steps that went into the design of 202 would be helpful.

So thanks, Alec. On your first question about moving 314 into pivotal studies for suprachoroidal delivery, we are making great progress in our Phase II evaluation with these dose escalations. We have already learned a lot with these first-ever suprachoroidal deliveries of gene therapy. Our collaboration with AbbVie allows for joint decision-making regarding these studies. It will depend on results from the cohorts and if they meet targets that indicate readiness for pivotal development.

Regarding RGX-202 and the potential for preexisting AAV8 antibodies, we are being diligent in screening out patients with substantial preexisting antibodies against AAV8. This is a focus for us given historical experiences, and our trial is excluding patients with measurable titers. We are studying the incidence and impact of these preexisting antibodies to understand their potential effect on efficacy better.

Our next question comes from Ellie Merle with UBS.

Just a little bit more color on the Phase III modification. Maybe can you just comment on any FDA and EMA recent interactions and just the latest feedback that you've gotten from them, particularly any feedback on the Phase III expansion as well as the latest feedback on manufacturing after the bridging study? And then just a broader question on the Phase III trials. I guess just according to the protocols, what kind of like data monitoring or interim analyses do you have ongoing in the study? I'm just curious, have there been anything in terms of the data review such as, say, an interim analysis, that may have prompted the decision to increase the study sizes?

Ellie, the opportunity to increase sample size was not driven by any regulatory interaction with the FDA. However, with any protocol amendment, these will need to be submitted for review. This action aligns with our internal assessments rather than feedback from authorities.

We haven't disclosed current patient enrollment specifics for DMD at this time, Ellie.

And our next question comes from Luca Issi with RBC Capital Markets.

This is Lisa on for Luca. First, maybe one on the fellow eye study. And just wondering, is the bilateral dosing going to be done at the same time? Or is there going to be a stagger between the doses due to the subretinal administration? And if there is a stagger, what gives you the confidence that the fellow eye will not have high levels of neutralizing antibodies against the vector? And I have another follow-up.

As part of clinical trials, we don't want to confound the parent study evaluating the study eye by having a fellow eye treated in proximity. In the fellow eye study, patients will generally be treated later, maybe a year or two years after their study eye treatment. While the subretinal delivery has immune privilege status, we need to demonstrate safety and tolerability in the fellow eye.

That's helpful. And then just maybe on DMD. Given your competitor's gene therapy that's close to approval, how do you think this will impact the regulatory path forward for your program? Will it still be possible to go after the accelerated approval pathway with microdystrophin as a biomarker if a full approval ends up being granted to your competitor? Any color there would be helpful.

It's hard to speculate too much, especially in rare disease areas and gene therapy, where certain patients will be excluded from receiving complementary therapies due to preexisting immunology. There’s a high interest from regulators to support multiple product options in these scenarios, and the agency is encouraged by surrogate biomarkers to predict clinical benefits. We view the emerging landscape of approvals as opening more opportunities than closing them.

Our next question comes from Mani Foroohar with SVB Securities.

This is Lillian on for Mani. Just a question in terms of the partnership on 314. So regarding the development and regulatory milestones, could you provide us with an update of where we are in terms of what potentially to be received in terms of subretinal versus suprachoroidal as well as wet AMD and DMD?

We haven't provided much specific guidance since we announced the collaboration. There's about $1.3 billion or $1.4 billion of potential outstanding development and commercial milestones that remain, with around half perhaps associated with development milestones for transitions into later-stage development for new indications, including the suprachoroidal platform.

Next question comes from Caroline Palomeque with Berenberg Capital Markets. Ken Mills, CEO, stated that they haven't provided much specific guidance since announcing the collaboration. There is approximately $1.3 billion to $1.4 billion in potential outstanding development and commercial milestones, with about half potentially linked to development milestones for transitions into later-stage development for new indications, including the suprachoroidal platform.

I think Ken, at one point, you mentioned that RGX-314 had a durability of over four years. So you have some patients that have shown that level of durability. I'm just wondering, is there a certain patient profile, aside from NAV negative, that you can speak to that tend to show higher durability? And then as a follow-up to that, can you speak to any FDA guidelines on gene therapy in the ocular space? Is there any discussion going on about what an acceptable threshold of durability is for approval?

When discussing subretinal patients showed durability of several years, we didn't screen based on preexisting immunity. So I cannot definitively state the antibody status for these patients. It’s a positive quality of our commercial opportunity; we later showed that suprachoroidal delivery wasn’t affected by preexisting immunity either. Regarding thresholds for approval, it varies, but a year seems to be the general measure for primary endpoints in pivotal trials. Durability data may play a role in regulatory review, but it’s likely that payer preferences will be more significant at the time of broader adoption.

And I'm currently showing no further questions at this time. This concludes today's conference call. Thank you for your participation. You may now disconnect. Everyone, have a wonderful day.