Good day. Thank you for standing by. Welcome to the REGENXBIO Inc.'s first quarter 2023 conference call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there'll be a question-and-answer session. To ask a question during this session, you'll need to press star one one on your telephone. You will hear an automated message advising your hand is raised. To remove yourself from the queue, please press star one one again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Patrick Christmas, Executive Vice President and Chief Legal Officer. Please go ahead, sir. Good afternoon, and thank you for joining us today. Earlier this afternoon, REGENXBIO released financial and operating results for the first quarter ended March 31st, 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 in the Management's Discussion and Analysis sections of REGENXBIO's Annual Report on Form 10-K for the full year ended December 31st, 2022, 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, May 3rd, 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. Excuse me. Good afternoon again, everyone. Thanks for joining us. I'm pleased to begin today's call, or continue today's call with a recap of our recent business highlights, as well as 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 31st, 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's been meaningful progress in the gene therapy industry lately, including growing understanding of gene therapy pricing models and the FDA's 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 with you how our 5 by 25 strategy is on track for advancing 5 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 update 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, also has been renamed ABBV-RGX-314. From now on, by the way, I'll 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. First, I wanna 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 take the opportunity 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 4-12 weeks for the duration of disease. First generation anti-VEGF treatments are not good. Emerging second generation anti-VEGF treatments are making an impact for some patients with longer incremental acting mechanisms. However, real-world evidence consistently shows us 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 disease well enough between doses. Patients, doctors, and clinics continue to struggle with the impact of the limitations of the current and the emerging anti-VEGF standard of care. Undertreatment is still leading to disease progression, damage to the retina tissue, and lost vision. 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 our 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're pleased to see this vision coming to life with today's announcement and the forthcoming global expansion. Where are we today? We think we're in a great position to optimize the opportunity for creating value with 314 for patients worldwide. We have the largest global clinical program for 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 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 REGENXBIO 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 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 meaningful reduction in anti-VEGF burden, with the majority of patients injection-free. 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, as a majority of patients currently on high interval standard of care could transition to a one-time gene therapy. There's opportunity to capitalize on additional market share from standard of care agents, biosimilars, and emerging longer interval treatments. Together with AbbVie, we're developing RGX-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 the potential to reach over 30 million patients with high unmet need in what is already calculated to be over a $14 billion global anti-VEGF market. Today, frankly, the utilization of anti-VEGF to treat diseases like early diabetic retinopathy is low. The treatment burden is high. Less than 1% of patients with early disease are treated with 1 intravitreal injections. We believe that there's a potential for RGX-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 DR in the U.S. alone, DR is estimated to be a potential $15 billion global market in the next decade, supported with the right treatment profile, such as a one-time treatment. 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 and 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 power of primary and secondary endpoints to enable these global regulatory submissions and labeling options. 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 and meaningful reductions in anti-VEGF burden. The majority of patients were injection-free following treatment with 314. 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 RGX-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 AAVIATE trial, a randomized dose escalation study evaluating RGX-314 in subjects with wet AMD. Cohort six is evaluating the third dose level with short course prophylactic ocular steroids following RGX-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 six 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 six in the second half of 2023. We also completed enrollment in cohorts four and five 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 four and five 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 IOI. 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 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 CureDuchenne's 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 REGENXBIO 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 mucopolysaccharidoses, 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 IDS 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 continued to be well tolerated across 15 patients. Patients receiving the pivotal program dose level continued to demonstrate the largest reductions in CSF GAGs, including heparan 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 IDS gene. We have completed enrollment of the Phase 1/2 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 1/2 trial at the 2023 WORLDSymposium in February, demonstrating that RGX-111 was well tolerated in 8 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 5 by 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. 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 31st, 2023, with cash equivalents, and marketable securities totaling $474 million, compared to $565 million as of December 31st, 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 a balance in cash equivalents, and marketable securities of $474 million as of March 31st, 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 on 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 need 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 that 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 are going to 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, 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 focus and a 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 5 by 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. Thank you. As a reminder, to ask a question, you'll need to press star one one on your telephone. To withdraw your question, please press star one one again. Please wait for your name to be announced. Please stand by while we compile the Q&A roster. One moment for our first question. First question comes from the line of Gena Wang with Barclays. Your line is now open. Thank you for the update. I have two parts of a question. First one is regarding the ATMOSPHERE and ASCENT upsizing by AbbVie. Wondering, can you remind us the powering assumption for the suite cohort study? Related question for manufacturing process from the in-house NAVXpress platform, what% of patients need to be dosed in order to clear regulatory requirement? My second question is regarding the DMD second half this year, the update, I assume the safety also will be very important update there. What kind of a safety profile will warrant the removal of the prophylactic Soliris treatment? Thanks, Gena. I'm gonna let Steve address the first question and circle back on the last two. Hi, Gena. Thanks for the questions. Taking the first part of your first question, so basically the powering concepts for the two pivotal studies, we have always, as is, you know, 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. That's really the aspect where 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. For that reason, we're very excited about increasing the sample size. As far as which endpoints, secondary endpoints we achieve greater power for, of course, with more patients, there's greater power across the board. Some of the ones that are potentially particularly interesting are the value drivers of decreased treatment burden. 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 require no injections? What proportion of patients require less than certain other thresholds? That's just to name a few. Again, we're excited at the opportunity that we have greater power across the board for these to help us in our plans. The second part of your first question, I think, related to the w as it the fellow eye? Or the No. It was just about manufacturing and just the inclusion for the NAVXpress process. Oh, okay. The inclusion. 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. Obviously, the bioreactor study is a direct comparator of the original process to the new process. We've also, in the case of suprachoroidal, actually been using bioreactor process almost out of the gate in NAV AAV8 and ALTITUDE. I think we feel like we're in a great place. Really what we're focused on right now with respect to the manufacturing work is the qualification lots that will support a commercial inventory, which will begin in 2023. With respect to RGX-202, you know, we're early in the process of obviously evaluating safety and tolerability. We said we'll have our first updates in the second half of this year. I think, you know, we're looking forward to reporting on information that would inform us not only about how to continue to navigate forward with respect to dose expansion or dose escalation, but also to potentially make some more informed decisions with respect to some of the protocols that we have in place in the sort of early safety assessments right now. It's too early to predict until we see the data, Gena Wang, exactly, you know, how things will navigate forward from here. We'll be relying on, you know, internal expertise and experience as well as the people that in the field guided us for the implementation of, you know, the use of the immune suppression protocols, including eculizumab, from a starting point. I mean, this was I think a very important sort of multi-stakeholder process that we went through to begin with, and I think we'll continue to sort of inform forward-looking decisions on the same basis. Thank you very much. Yeah. Thank you. One moment for our next question, please. Our next question comes from the line of Dane Leone with Raymond James. Your line is now open. Thanks for taking the questions. 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. Just trying to understand the nuance of what may have changed in the agreement. Secondly, could you opine a little on some of the poster presentations that you have coming up at ASTCT? Curious to know how serious we should take the GA program that's being presented there and, you know, if you do have a view on terms of bringing that into the clinic, what the timeline might be for that. Thank you. Thanks, Dane. Appreciate the question. I think on the agreement side, I think the message is landing the way we intended it. I mean, we've said, you know, since the beginning of 2023 that under our original collaboration, you know, AbbVie has transitioned to taking on the majority of costs for the program overall, and that it was also originally expected for the IND transfer to occur. That happens to now be, you know, overlapping with the announcement today of the global expansion work that we're doing with respect to ATMOSPHERE in a sense. This is not anything that was new with respect to the original collaboration understanding. These are all sort of programmatic things that are being implemented now that we're about a year or maybe over a year into the collaboration that of course, you know, took time between the teams to execute on. With respect to the ASGCT presentations and posters, we're excited to, you know, as always be able to share a lot about, you know, the research that goes on within REGENXBIO across multiple different therapeutic areas. We've been, and continue to be focused on targets that have significant unmet need and are significant populations. You know, obviously we have a curiosity and a strong interest with respect to indications that can extend into areas that we already work in, including in and around retina. You know, I don't think that, you know, we're saying anything more than that right now. It's just that we have a really strong research engine with respect to work that's led by Olivier and his team. It's very much in contact with work that we do in the clinic, both on the device side, on the technology side, and on the clinical experience side. You know, we've said all along that we're gonna continue to look for high-value indications to add to our pipeline. This is an opportunity for us to show some of the basic research that's going on, but certainly not any specific guidance about any new INDs that we're announcing today. Thanks. If I could just add 1 follow-up to that. I was excited to see the addition of the bilateral cohort being run. Is that an 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 in the pivotal program to allow bilateral treatment? Thank you. Hi, Dane. Yeah, this fellow eye protocol allows patients who've been treated in either ATMOSPHERE or ASCENT to have their fellow eye treated with RGX-314 or 314. Sorry. This actually is as per plan from way back 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 so that we've treated both eyes, so that would be allowed in the label. Excellent. Thank you. Thanks, Dane. Thank you. One moment for our next question, please. Our next question comes from the line of Vikram Purohit with Morgan Stanley. Your line is now open. Hi, everyone. Thanks for taking our call. This is Gospel on for Vikram. 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/or pivotal studies for the suprachoroida l delivery of wet AMD? The second one is for the RGX data expecting in second half of this year. Would you expect to release this data through a top-line release, or is there a medical conference or venue that could be suitable for it? Yeah. Thanks, Gospel. I think, I can hit these and then if Steve has more to offer. I don't know that we see, you know, a direct impact with respect to the regulatory path. We're very advanced with subretinal, and I think as we were just talking with Dane about including things like fellow eye studies and sort of preparations for, you know, qualifying lots for supporting commercial manufacturing. I think we're, you know, our view is that we're hurtling towards, you know, important milestones for regulatory approvals that we've given guidance on now, both in the US and outside of the US for the subretinal approach. With respect to suprachoroidal, we're gonna have, you know, we're still in sort of dose-ranging mode in phase IIs. I think of course, you know, it's strongly influenced by the same pharmacology. I mean, RGX-314, obviously, its activity, its ability to show biological activity and treatment effect in a, you know, kind of first product with the subretinal delivery, I think has a strong indirect influence. You know, right now, I don't see any direct relationship between our forward-looking plans for how we complete the work to support the filings and approvals of subretinal and where we are with suprachoroidal. Again, they're, you know, they're related. They're tethered, of course, because of the same pharmacological agent. Otherwise, they're as we've been guiding for the last, you know, year or so. With respect to AAV8 and ALTITUDE, you know, usually those are decisions that are made closer to the point in time when the team has reviewed the data and is able to sort of assess opportunities for presentation. I think our practice and our view has been to do these at medical conferences, and I think that AbbVie generally shares that view when we come together on these topics. I think that's the most meaningful guidance we can, in addition, give there right now. Yeah. Okay. Thank you. One more question to ask, please, for the RGX-202 data for Duchenne. I was wondering, for this data release, is it gonna be a top-line release or a medical conference? Haven't decided yet. I think, again, you know, it'll depend a little bit on the timing. Certainly, we keep our eye on conferences that would be, you know, appropriate venues for that, just as we do for the, you know, retina work. We, you know, That will be a decision that will be made, again, a little bit closer to, well, frankly, in the second half of the year, Gospel. Thank you very much. Thank you. Thank you. One moment for our next question. Our next question comes from the line of Alec Stranahan with Bank of America. Your line is now open. Hey, guys. Thanks for taking our questions. Just two from us. Appreciate all the color on 314 and the updates under 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, and is this go, no-go now under AbbVie's full discretion? Secondly, on DMD, given that you're recruiting patients into AFFINITY-BEYOND, is there an expectation that a subset of DMD patients could have preexisting AAV8 antibodies that could lower efficacy of 202? A refresh on any of the mitigation steps that went into the design of 202 would be helpful. Thank you. Thanks, Alec. On your first question on 314. For suprachoroidal in-office delivery, we're making great progress in our phase II evaluation with these dose escalations in both of the studies for wet AMD and DR. We're learning a lot. We've already learned a lot with these first ever suprachoroidal deliveries of gene therapy. And we're excited that we have the opportunity to evaluate short course ocular steroid treatment to further mitigate any risks of inflammation. It's really gonna depend on readouts from these existing cohorts that we're gonna disclose at least initial results later this year. I think the process we and AbbVie go through, it is a joint process with our joint committees, where we collaborate very closely on evaluating any new data cuts that come out. It really comes down to at what point do we feel we potentially could be meeting target profiles for either of these indications that then triggers when we believe we could go into pivotal development for either of those indications. I think that we have, you know, a view that we're well aligned with AbbVie at this stage in terms of, you know, being incentivized to move as judiciously and as quickly forward as we can based on the data that we see. We're, you know, in the process, having just fully enrolled both ALTITUDE and AAV8 with the expansion cohorts to have opportunities to look at new data from those cohorts as well as continuation of data we've already reported. I think it'll be a good point in the second half of the year, to revisit that question and sort of establish, where we are with respect to that process overall. On the 202 side, I think I understand your question, which was, you know, we've got this AFFINITY-BEYOND, you know, study going on, looking at incidence or prevalence of, preexisting, AAV to antibody titers in patients. Absolutely, I think as a class, you know, AAV microdystrophin products, I think this is a focus for all of us. You know, we know this from other experiences in other trials that we've run, including our AAV8 intravenous trial in HOFH. Our peers are all generally in clinical phase, screening out patients with measurable or certainly above a certain threshold, titers of preexisting antibodies to their specific capsid. I think we're all looking to be able to characterize that and evaluate it commercially. There's a lot known about AAV8. It actually is already from studies that have been published and that we've worked on, known that it's a relatively low prevalence with respect to preexisting. We want to study it specifically in this disease basis too. I know that, you know, if you were working with AAV9 or another AAV8, you know, you'd be focused on the same thing. Right now, our trial is excluding patients who might have antibodies to AAV8 for purposes of enrolling in the treatment study, but we're building this body of evidence to understand more, both clinically and commercially, how we keep navigating this program specifically with AFFINITY BEYOND. Very helpful. Thank you. Thank you. One moment for our next question. Our next question comes from Ellie Merle with UBS. Your line is now open. Hey, guys. Thanks so much for taking the question. just a little bit more color on the phase 3 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 3 expansion as well as the latest feedback on manufacturing after the bridging study? Then just a broader question on the phase 3 trials. I guess just according to the protocols, I guess, what kind of like data monitoring or interim analyses did you have ongoing in the study? I'm just kind of curious, had there been anything in terms of the data review, such as say an interim that may have prompted the decision to increase the study sizes? Thanks. Hi, Ellie. As far as any regulatory FDA or other interactions, this opportunity and the action to increase the sample size was not driven by any FDA interaction. Though of course with any protocol amendment these get submitted. This is in line with the protocol and has been submitted to the FDA. There's no issues there. As far as the monitoring, you know, I remind this is a masked ongoing study, so there's certainly no opportunity to be looking at any efficacy results in this. There's just really the standard medical monitoring that's applied in this kind of study. Understood. Then just a question in terms of DMD. Can you maybe just comment how many patients you've enrolled and dosed so far? We haven't updated on that today, Ellie. Okay. Understood. Thanks, guys. Thank you. One moment for our next question. Our next question comes from the line of Luca Issi with RBC Capital Markets. Your line is open. Oh, great. Thanks for taking our questions. This is Lisa on for Luca. First maybe one on the fellow eye study. 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? 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? I have another follow-up. Thanks. As you can imagine, as part of clinical trials, we don't wanna confound the parent study evaluating the study eye by having a fellow eye treated in any type of proximity. In the fellow eye study, this will generally be patients who are getting their fellow eye treated sometime later, you know, maybe a year or two years after having their study eye treated. In the real world we know, for example, historically with Luxturna, you know, totally different disease setting and other considerations, the concept of timing them closer together, which can, you know, have the added safety consideration of at least theoretically minimizing induced immunogenicity. Though one of the benefits of subretinal, of course, is the relative immune privileged status. We anticipate good safety and tolerability in a fellow eye. You raise a good point. We have to actually demonstrate that given that treatment, even with subretinal delivery, you can have at least the asymptomatic antibody response. This will be our opportunity to evaluate that. That's helpful. Thanks. And then just maybe on DMD. You know, given your competitor has a 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 the biomarker if full approval ends up being granted to your competitor? Any color there would be helpful. Thanks. Yeah. Thanks, Lisa. I mean, I think it's really hard to speculate too much, especially in these, you know, rare disease areas, including in gene therapy where. You know, it's gonna be known that there are kids that are gonna be excluded from the potential to receive certain of the gene therapies because of the topic that we were talking about with one of the analysts before that, you know, certain patients are gonna be excluded for accessing certain therapies, especially systemic therapies, because of preexisting immunology. Then they may be able to receive an alternative therapy that's, you know, up for approval or in development. In general, you know, I think we've seen a great interest on the part of regulators and the community to support, you know, many product alternatives in those types of circumstances where, you might see, you know, populations that have access issues or, you know, just generally with respect to responsiveness. We're really excited and encouraged about the views that, you know, the agency is taking on concepts of accelerated approval and the use of surrogate biomarkers to predict clinical benefit. We like the position that we're in with respect to being in a class of medicines that is under review because we are gonna learn a lot, in, nowadays, not even weeks or months anymore. I would, you know, I would say that we view that there's a lot of options and they will be informed by some of the process and the decisions. My sense is that it opens more doors than it closes. That's helpful. Thanks for taking our questions. Thank you. One moment for our next question. The next question comes from Manny Foroohar with SVB Securities. Your line is open. Yes, good afternoon. This is Lili Nsongo on for Manny. Just a question in terms of the partnership on RGX-314. Regarding the development and regulatory milestone, could you provide us an update maybe of where we are in terms of what's potentially to be received in terms of subretinal versus suprachoroidal, as well as wet AMD and DME? Yeah, I don't think we've given too much specific guidance since we announced the collaboration. I think we emphasized that, there's about $1.3 billion or $1.4 billion of potential outstanding development and commercial milestones that remain with, I think around half of that potentially being associated with development milestones for transitions into later stage development for new indications or including, the suprachoroidal platform. I think, you know, those will be the things that would be opportunities for, you know, nearer term access, pre-commercial, in particular with respect to development milestones. You know, I think as we get into periods of time where those evaluations are ongoing, we sort of update interpretations of data, we can perhaps give some more clarity. At this time, we, you know, as I think Vic spoke to with respect to even our cash guidance, we're not including any of those milestones right now in any of our plans. It's very not typical for us to do that. We're being, I think, very conservative about the cash guidance that we're giving, even though we have, you know, known upcoming data readouts with respect to certain of these programs that could inform these things. Thank you. Thanks. Thank you. One moment for our next question. Our next question comes from Caroline Palomeque with Berenberg Capital Markets. Your line is open. Hi. Thanks for taking the question. I think, Ken, at one point you mentioned that RGX-314 had a durability of over four years. You have some patients that have shown that level of durability, and I'm just wondering, is there a certain patient profile, I mean, aside from NAb negative, that you can speak to that tend to show a higher durability? And then as a follow-up to that, can you speak to any FDA guidelines on gene therapy in the ocular space that, you know, is there any discussion going on about what an acceptable threshold of durability is for approval? Thanks. Yeah, Caroline, when we're talking about subretinal, first of all, these are all patients that we didn't even screen on the basis of preexisting immunity. You know, I'm not even sure that we know that these patients, several of them are out, you know, three, four years with durability and they could be NAb positive or not. I don't even know that I've seen that data per se. You know, that's a very positive statement to make about the commercial opportunity, by the way, for subretinal, that it has no impact. We later showed that it seems that suprachoroidal also is not impacted by preexisting immunity. This is all a very different space than intravenous delivery. I think with respect to thresholds and sort of interests that the agency has, and I think that it's multilayered. I think for approval, you know, it's kind of durability is something that I think is, you know, kind of on a shorter interval. I, you know, I would say a year, which is, you know, basically the measures of our, you know, primary endpoints in our pivotal trials, as well as, you know, how we're studying things even at early phases is, you know, you accrue enough patients with respect to a year and both on a primary and a safety basis, I think you're setting yourself up for approval with respect to the agencies. I think the question really comes to bear on the payers and the providers and the adoption of the treatment overall. And this is, you know, and we're highlighting today, I think how much further along, how much deeper, how much broader our program is and will continue to be, you know, in wet AMD and in diabetic populations with respect to 314 across additional devices and how important that information is for global development and ultimately global commercialization. You know, while the FDA, a group like the FDA, I'm sure they're gonna be happy when a package comes in with three, four year data, you know, and it'll give them more confidence. You know, I'm not sure it's going to be something that's sort of it's heavily weighted. I think when we're in the payer environment and we're in the with this globalization, when we're in the, you know, health technology assessment environment, these things are gonna become, I think, incredibly important. I think the differentiation for where we are with 314, our view is, really meaningful and, you know, one of confidence. Great. That's very helpful. Thanks. Thank you. Thank you. 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.