REGENXBIO Inc. Q4 FY2024 Earnings Call

Welcome everyone to the Fourth Quarter and Year End 2024 REGENXBIO Earnings Conference Call. At this time, all participants are in a listen-only mode. To ask a question during the session, you'll need to press star one one on your telephone. To withdraw your question, please press star one one again. Please be advised that today's conference is being recorded. At this time, I'd like to turn the conference over to Patrick Christmas, Chief Legal Officer of REGENXBIO.

Good afternoon, and thank you for joining us today. Earlier this afternoon, REGENXBIO released financial and operating results for the fourth quarter and year ended December 31, 2024. The press release is 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 section of REGENXBIO's annual report on Form 10-Ks for the full year ended December 31, 2024, and comparable risk factor sections over 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, March 13, 2025; 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 represent or project financial positions or operating results of the company. Actual results may differ materially. I'll now turn the call to Curran Simpson, President and CEO of REGENXBIO. Curran?

Thank you, Patrick. Thank you everyone for joining us today. 2025 is a transformational year for REGENXBIO. We are off to an exciting start. We've submitted our first BLA and expect our first FDA approval in the fourth quarter for RGX-121, which is our treatment for boys with Hunter syndrome. We will build on this momentum by advancing our diabetic retinopathy program to the pivotal stage this year, then head into 2026 with potential BLA filings for large opportunities including RGX-202 for Duchenne muscular dystrophy, and ABBV-RGX-314 for wet AMD. We are in a strong position as we prepare to launch multiple first or best-in-class gene therapies and have robust commercial capabilities and global partners. This is all with a view to sustainable profitability and is the result of fifteen plus years of gene therapy leadership. On today's call, I will review our recent business highlights and outline a vision for what we believe will be catalyst-rich years ahead. Then our chief medical officer, Dr. Steve Pakola, will summarize our clinical progress before handing it over to Mitchell Chan, Chief Financial Officer. Mitch will provide an overview of our financial results and share the many potential non-dilutive capital sources ahead. I'll then make some closing remarks before we open for Q&A. Starting with our recent exciting news in MPS, we are thrilled to have completed the submission of the BLA for RGX-121 under the accelerated approval pathway and partnered with Nippon Shinyaku for both of our MPS programs. This partnership marries our collective strengths, REGENXBIO's development and manufacturing expertise, with Nippon's experience in successfully commercializing rare disease products. Our teams are planning for potential approval of RGX-121 for MPS II in Q4 2025 and are working diligently to prepare for the commercial launch. Along with enabling access to these important medicines for patients in the US and Asia, this partnership is strategically significant to REGENXBIO. As Mitch will share, this agreement provides meaningful potential milestones and revenue for us. The potential approval of RGX-121 also provides strategic value for the rest of our pipeline as we receive commercial licensure of our manufacturing facility prior to launching in our larger programs including RGX-202 for Duchenne. Moving to RGX-202, I am pleased to report that our pivotal study is advancing rapidly. Our unique second-to-market or fast-follower opportunity is on track for a mid-2026 BLA filing. Recent updates have indicated tremendous interest in the patient community for new treatments with RGX-202 as a valued option. Input from our growing investigator community supports our belief that RGX-202 has the potential to be a preferred and differentiated treatment option. I'll remind you that RGX-202 is the only investigational next-generation DMD gene therapy in pivotal study with both robust microdystrophin and functional data available. The pivotal trial of RGX-202 is rapidly enrolling approximately thirty ambulatory patients aged one and over. I'm pleased to share that this pivotal trial is nearly half enrolled and we expect to complete enrollment this year. We are also on track to submit a BLA under the accelerated approval pathway by mid-2026. We expect more than half of the prevalent population to remain untreated through the next few years and this large population will need more than one treatment to serve all Duchenne patients. That's why we're confident in the rapid progress we've made thus far and our path to delivering a potentially preferred gene therapy option. Also, let me remind you that we are commercial-ready when it comes to manufacturing 202. Our in-house state-of-the-art suspension-based bioreactor process is currently producing 202 for our pivotal study with industry-leading purity levels of more than eighty percent forecasted. Our manufacturing innovation center can produce 2,500 doses of RGX-202 per year. As we continue to aggressively accelerate BLA enabling activities and commercial planning, we will share more meaningful updates. Specifically, we plan to share additional positive phase one/two biomarker data later this month at MDA, as well as updated phase one/two functional data in the first half of this year. With positive biomarker and functional data in hand, encouraging interactions with FDA and commercial-ready manufacturing, we believe our second-to-market position in Duchenne remains strong. Lastly, I will highlight a few updates on ABBV-RGX-314. This is our global AbbVie partner retinal franchise that is advancing in late-stage studies. As announced with AbbVie in January, data from the pivotal studies evaluating subretinal 314 in patients with wet AMD are expected in 2026. We expect to complete enrollment of both of these pivotal studies this year. In our diabetic retinopathy program, evaluating in-office suprachoroidal delivery of 314, we held a successful end of Phase Two meeting with the FDA in the fourth quarter of 2024. We are now planning a pivotal program with AbbVie to support future global regulatory filings. As we have said before, wet AMD and DR are very large commercial opportunities. And 314 represents a potential alternative for the patients losing vision with today's standard of care. Importantly, we will be entitled to additional milestone payments that are part of this $1.8 billion collaboration with AbbVie. In summary, we are excited for and well-positioned to deliver on the opportunities ahead of us to drive value for patients and shareholders. With that, I would now like to turn the call over to Steve for an update on our clinical programs. Steve?

Thank you, Curran. I'll start with RGX-202, a potential one-time gene therapy for the treatment of Duchenne. RGX-202 is the only microdystrophin construct to include the C-terminal domain, making it closest to naturally occurring dystrophin. In preclinical studies, microdystrophin with the CT domain was shown to better protect the muscle from contraction-induced damage associated with muscle breakdown in Duchenne. In November, we announced the initiation of the pivotal phase of the AFFINITY Duchenne trial evaluating 202 at a dose of 2E14 genome copies per kilogram in approximately thirty ambulatory patients aged one and older. We also recorded positive safety and efficacy data from the phase one/two portion of the study. The data disclosed in November included positive functional outcomes from the first five participants in the Phase one/two portion at nine and twelve months. We also shared microdystrophin and other compelling biomarker data from eleven patients. In summary, the results showed 202 recipients exceeded external natural history control and established benchmarks for clinical outcomes. Specifically, we observed functional improvements in all patients treated with dose level one and dose level two at twelve and nine months respectively. Consistent robust expression, transduction and localization of our differentiated 202 microdystrophin in the muscle and also a favorable safety profile observed at both dose levels. There were no serious adverse events or AEs of special interest, which is truly outstanding in the landscape of Duchenne gene therapy. As we've discussed, we've taken a thorough proactive approach to safety based on input and partnership with treating physicians and the patient community, as well as learnings from the field at large. Our immune suppression regimen including a short course of eculizumab combined with our novel microdystrophin and leading product purity levels may be contributing to this positive safety profile. These positive clinical results further strengthen our belief that 202 has the potential to serve as a best-in-class gene therapy for Duchenne muscular dystrophy. We look forward to sharing additional biomarker data at the MDA meeting in the coming days including the first microdystrophin data from our cohort of patients under four years old. As Curran mentioned, the pivotal study is ongoing and advancing rapidly. The one to three age group represents a significant portion of the prevalent population of Duchenne patients yet this group has no access to approved gene therapy. With pivotal enrollment nearly halfway completed, we look forward to continuing to work with physicians and the Duchenne community to complete enrollment this year and report top-line data in the first half of 2026. Now on to our retina franchise, ABBV-RGX-314 which is being developed in collaboration with AbbVie to treat wet AMD and diabetic retinopathy or DR. I'll start with 314 for DR being evaluated in the phase two Altitude trial using in-office suprachoroidal delivery. Like wet AMD, DR is a progressive disease that causes vision loss, and ultimately blindness if not treated appropriately. It is a leading cause of blindness in working-age adults. As we've shared, we have completed our end of Phase Two meeting with the FDA and are now working actively with AbbVie on plans for our phase three clinical program. The program is expected to support global regulatory filings with the goal of preserving vision for millions. We've previously expanded the broad multi-indication global potential of 314 by initiating a new cohort in the Altitude trial. This cohort is enrolling patients with diabetic macular edema or DME, a vision-threatening complication of diabetic eye disease. In wet AMD, we are evaluating 314 via two different delivery forms: subretinal and suprachoroidal. Within subretinal, we have two ongoing pivotal trials, Atmosphere and Ascent in the US, Europe, and Japan. These trials continue to progress well as we announced in January enrollment of both pivotal trials is expected to complete this year and we expect to share top-line data in 2026. Overall, we continue to be encouraged by 314's progress. I'd like to particularly highlight the safety profile observed in our suprachoroidal program. In more than 180 patients treated in-office, we're seeing a differentiated safety profile particularly in the setting of short-course seven-week prophylactic steroid eye drops, a significantly shorter regimen than those used in other gene therapy trials. This continues to support the potential of 314 as a meaningful treatment option for patients and physicians. Finally, onto our MPS program. It's an incredibly exciting time for REGENXBIO and the Hunter syndrome community with the submission of our BLA for RGX-121. This filing is based on data from the CAMPBELL trial which met its primary pivotal endpoint with high statistical significance. Patients treated with 121 achieved decreased CSF levels of heparan sulfate D2S6, a key biomarker of brain disease activity, to below maximally attenuated disease levels approaching normalization. Our BLA using the accelerated approval pathway is based on D2S6 as a surrogate endpoint reasonably likely to predict clinical benefit. We also previously reported that eighty percent of patients who received the pivotal dose discontinued enzyme replacement therapy or remain treatment-naive, as well as neurodevelopmental skill acquisition, up to four years post-dosing. This is a meaningful update for patients and families whose only option today is weekly enzyme replacement therapy that does not address the neurocognitive decline of this disease. 121 is well-positioned to be the first gene therapy and one-time treatment for Hunter syndrome that can address neurocognitive decline. We anticipate a potential FDA approval decision in the second half of 2025. To conclude, we continue to make significant progress with data updates and trial progression across all programs in our pipeline. Lastly, I'd like to thank the patients, families, clinicians, and patient advocacy representatives who have been involved in and supported all of these trials. With that, I'll turn the call over to Mitch to review our financial guidance. Mitch?

Thank you, Steve. REGENXBIO ended the quarter on December 31, 2024, with cash, cash equivalents, and marketable securities of $245 million compared to $314 million as of December 31, 2023. The decrease was primarily driven by cash used to fund operating activities during the twelve months ended December 31, 2024, partially offset by $131 million in net proceeds received from an upsized public offering of common stock and pre-funded warrants completed in March 2024. R&D expenses were $209 million for the year ended December 31, 2024, compared to $232 million in 2023. The decrease was primarily attributable to decreases in headcount and preclinical activities. We expect the balance in cash, cash equivalents, and marketable securities of $245 million as of December 31, 2024, to fund our operations into the second half of 2026. This cash runway guidance is based on the company's current operational plans and excludes the impact of any future potential commercial revenue associated with RGX-121. If we include additional non-dilutive financing, we expect the cash runway to potentially extend meaningfully beyond 2026. For instance, some examples of our non-dilutive financing options include our expected DR milestone payment from AbbVie, development milestone payments from Nippon Shinyaku, conversion of our Zolgensma royalty income, and the potential monetization of our priority review voucher on RGX-121 if approved. Collectively, we have many non-dilutive financing optionality that could extend our cash runway well beyond the second half of 2026. In summary, we feel we are in a strong financial position as we near. With that, I will turn the call back to Curran to provide final thoughts.

Thanks, Mitch. As you heard today, there's strong momentum across our pipeline as we advance towards key milestones. To recap, we have officially submitted our first BLA and closed an important partnership with Nippon Shinyaku for our MPS programs. We look forward to a potential FDA approval of RGX-121 this year. The pivotal study of RGX-202 is moving rapidly and we believe remains well-positioned to potentially serve as the next and preferred gene therapy in Duchenne muscular dystrophy. We plan to share additional positive biomarker data later this month followed by updated functional data. And with enrollment nearly halfway through, we expect to complete enrollment of the pivotal study this year and share top-line data in the first half of 2026. Our partnership with AbbVie is advancing towards multiple large global commercial opportunities. We expect to complete enrollment of two global pivotal trials for subretinal wet AMD and are working with AbbVie on a pivotal study in diabetic retinopathy in 2025. As we look towards the next nine months and beyond, we are well-positioned to deliver on multiple late-stage opportunities. Our programs are demonstrating beneficial differentiation against standard of care and available treatments. Each of our assets represents one-time treatments with the potential to transform the trajectory and management of disease for patients in need of new and better options. We look forward to sharing additional updates on our plans and achieving our critical milestones this year. With that, thanks for everyone for your time today. I'll turn the call over for questions. Operator?

Withdraw your question. Our first question comes from the line of Judah Frommer with Morgan Stanley. Judah, your line may be on mute.

Hi. Can you hear me now? Yep. Thanks. Congrats on the progress here. Just one on cash runway and one clinical question. So I was hoping maybe you could delve a little deeper into the components of non-dilutive financing that are still available. And maybe you could give us kind of some internal insights into probabilities around realizing those. We do get questions around the PRV and then anything that could get in the way of the AbbVie milestone coming through for DR. And then just on the clinical side, another question we've been getting just expectations around potentially going to an adcom for 202 once you have the full dataset. Thanks.

Yes. Thank you, Judah, for the question. Regarding non-dilutive options, as I kind of mentioned, it really comes in three different flavors. The first one is the DR milestone that we expect to receive in the second half of this year. That really is gated upon the first patient dose, and Steve and Curran could definitely speak to the clinical program timings and so forth. But that's really the potential risk to it is more of a timing issue than anything else because our expectation is that they will move forward. Regarding the PRV, I think the question here is when do we receive a potential regulatory approval. Upon regulatory approval, that's when we're eligible to receive our priority review voucher; we could then choose to monetize it at our discretion. So I think that's more of a regulatory approval risk than anything else, which we do not expect to have anyways at this moment in time. And the other non-dilutive financing option really is on the potential of Zolgensma royalties stream that may revert back to us once we hit the HGR cap of $300 million; that royalty stream does revert back to us. Again, it's hard to predict future revenues from Zolgensma given that it is promoted by a third party, Novartis here. But once that we reach the cap, that revenue stream will revert back to us forward to the revenue stream.

Hi, Judah. It's Curran. I can talk a little bit about just the PRV and probabilities of success. I think the fact that we've had a pre-BLA meeting with FDA and they have reviewed the pivotal data really helps in terms of de-risking. They've seen our approach. And while, of course, it's a regulatory review and that has risk associated with it like any, we feel like we're in a really good place particularly because, over time, MPS II and therapies like ours have been referred to as good fits for an accelerated approval pathway. So I do expect this to be a high probability event in terms of receiving both an approval and the PRV. And that's in line with all the FDA interactions we've had. I'll let Steve comment a bit on DR, but I think the events that are occurring for DR now are really just regulatory discussion with AbbVie in the lead in terms of conducting those meetings. We talked last fall about the end of Phase Two meeting with FDA and related that that meeting was very positive in terms of our approach. And we've also discussed that they're also seeking regulatory advice ex-US, and that's an ongoing process. But we feel like two key things: the data's strong, and so far the feedback's strong. Again, pointing towards a positive movement towards the DR pivotal this year.

Sure. Hi, Judah. I think as Curran mentioned, we're very happy with the end of Phase Two meeting with the FDA. AbbVie's always been very interested in global advancement and really getting access to 314 globally. That's one of the reasons we struck the deal with AbbVie. So not surprisingly, for a global diabetic retinopathy plan, they do want to get EMA and feedback from Japan. So those are some of the aspects that we want to tidy up before we can give any more details on the plan. But fortunately, we have the benefit of precedent in treatment of diabetic retinopathy to know what to expect in terms of a regulatory path here. So we feel this is pretty de-risked based on our regulatory discussions today. You also had a question on an advisory committee, which I believe is probably related to 121 since we announced completion of the BLA submission. We don't know; it's not the kind of thing we can say with a hundred percent certainty either way. As of now, we don't see a significant issue anywhere that would suggest one is needed. If one comes our way, we'll be ready for it. So I think with any development program at this stage, you plan in case you may need it. If we have one, we'd be very confident given the compelling data we have and the different stakeholders that could be a part of weighing benefit-risk for the product. But as of now, we don't know.

Thanks.

Our next question comes from the line of Gena Wang with Barclays.

Thank you for taking my questions. I apologize if this question was already asked. My phone got dropped, so I missed the previous question. I have two questions. One is regarding the NDA update. Just wondering how many patient data from one to three-year-old should we expect to see? And also, given the younger patient age, should we expect to see higher protein expression? And related question, any thoughts regarding lowering age to zero, given mention that you were starting a cohort between zero and eighteen months. And then my second question is regarding the Altitude DME cohort. Just wondering what will be the timing of data update? And also number of patients and type of data you will share with us.

Great. I'll take the first one, and then I'll let Steve answer the second one. We're planning to update at MDA likely one patient in the one to four cohort in terms of their microdystrophin value. Based on the emerging database that we're gaining on age versus microdystrophin, it's a fair expectation to expect higher microdystrophin levels in younger patients. But, obviously, we'll save the specifics for the conference itself. We're seeing a general trend that younger patients will have higher microdystrophin numbers, both in our study and other studies in the public domain.

Hi, Gena. Thanks for the question. So Altitude, our diabetic retinopathy study, where we've already shown very solid data in patients without DME, is why we're excited with AbbVie to go into pivotal. You referred to the DME cohort, which we currently have enrolling. Enrollment is progressing quite nicely. We haven't given any guidance on when we would read out, but it's safe to say that when we do, you could look for the typical things that we've looked for in a wet AMD population but with different reference points. In DME, you care about visual acuity, and you also care about disease activity assessed by retinal thickness on OCT. And the third part of the triad is whether you can achieve good disease control and good visual acuity with a reduction in the need for injections — i.e., treatment burden. So we would report on all three of those as well as safety.

Thank you.

Our next question comes from the line of Mani Foroohar with Leerink.

Hey, guys. You have Ryan on for Mani. Thanks for taking our question. So maybe just two. Can you talk about what you're seeing in terms of pace of enrollment for the DMD pivotal trial and whether you expect this to accelerate as the year goes on as you activate new sites and share more data in the first half of the year? And then maybe just on the younger patient enrollment within DMD, have you moved on to enrolling those patients in the pivotal trial yet, or are you still enrolling that separate cohort from the phase one/two trial?

Thanks. We're seeing really encouraging enrollment in the Duchenne study. We know that from screening logs and what we're seeing at sites as sites are activated that there's a significant number of patients going through screening. We do expect enrollment to accelerate primarily because we're increasingly adding sites to the study. So overall productivity of the study will continue; it'll be a nonlinear enrollment curve. We're optimistic about meeting our guidance to conclude enrollment this year, and we're aiming to exceed that guidance by finishing sooner.

The other interesting aspect is it's not just increased sites, which certainly will help as we bring more sites on board, but we saw a lot of interest after our November functional data update. We've heard from patient advocacy and investigators that there's a lot of families that had been waiting on the sidelines for a next-gen gene therapy as long as they could see some functional data. So having the nine and twelve month data has really bolstered our case across clinics. We're in good shape. Regarding the younger patients, the one to three-year-old age group: we look forward to providing the initial microdystrophin data in that age range. And by the way, we have seen with other programs that younger patients tend to have higher microdystrophin levels. One of the massive unmet needs is in the older patients where other programs haven't seen high microdystrophin levels. We're excited to treat broadly across the age range, which is why we're enrolling one year old and up. Any patients enrolled now who are one and above will be included in the pivotal. We're very excited to enroll across the one to three, four to seven, and eight and older cohorts.

Thanks, guys.

Our next question comes from the line of Luca Issi with RBC Capital Markets.

Oh, great. Thanks so much for taking our questions. This is Lisa on for Luca. Just on the DMD program, can you remind us if you are measuring cardiac endpoints like left ventricular ejection fraction or cardiac biomarkers like troponin I as part of the AFFINITY study? And if so, could these be a meaningful way to differentiate your program further from Elevidys? And I have one question on wet AMD. On the subretinal study, I'm just curious if you are considering maybe cutting the enrollment a bit short in order to accelerate the readout timeline. We know the wet AMD space is very competitive, and there are also two long-acting TKI studies that are anticipated to read out in 2026. From experience, being first to market does matter. Any color here on DMD or those subretinal pivotals would be appreciated. Thanks so much.

Great. I'll let Steve comment on retina, but regarding cardiac: from our preclinical data, when we looked at biodistribution we expect good distribution not just to peripheral muscle but to heart and lung. That's represented in studies like the treadmill test for mdx mice. In terms of differentiating on cardiac outcomes, that will be more of a longer-term outcome and will be monitored over time. We don't expect to see dramatic cardiac improvement in very young children over a short timeframe, but it's certainly part of our monitoring and evaluation.

Hi, Lisa. The reasons Curran mentioned, we feel very positive about the potential to have a benefit for Duchenne children not just based on skeletal muscle but also cardiac manifestations. Context to give is that decreases in cardiac function typically occur at an older age than the typical functional assessments we look at in younger groups. It's really as boys advance into the teen years that you see cardiac deterioration. We're excited we're seeing very high and consistent microdystrophin expression in older boys, which bolsters confidence. We do measure ejection fraction and use echocardiography and MRI; MRI is more accurate and sensitive. We also monitor troponin levels. But it's not meaningful to look for cardiac benefit while cardiac function is normal; it's more detectable once patients are older and start to show decline. Regarding wet AMD subretinal pivotal trials, we would not consider cutting enrollment short, and AbbVie would not either. One of the key reasons we increased the size was to be able to go global. With a partner like AbbVie, we want to do things right and fully characterize efficacy to inform the clinical community and regulators. We look forward to completing enrollment this year and having results next year. There is trial competition in wet AMD, but we see a paradigm shift: potentially preventing the need for injections for the majority of patients versus incremental improvements in injection schedule. That's a strong differentiator and we're pleased to be moving forward.

One thing to add: we are cognizant of timing and moving quickly to a BLA filing. AbbVie will be preparing and filing the BLA; they have a large regulatory organization and a strong track record of speed to BLA from top-line data. We'll work with them to move as fast as possible while doing it the right way.

Alright. Thanks so much for taking the question.

Our next question comes from the line of Annabel Samimy with Stifel.

Hi. Thanks for taking my questions. Just following on the regulatory discussions for DR: are there any specific key areas of difference between the US and the OUS regulators that we should be thinking about? I know that the pathway is pretty clear for the US. I'm curious about OUS. And then on DMD, for the upcoming data disclosure at MDA, will we be seeing just a follow-up from patients you've already disclosed, or will we see new patients among the eleven that have already been treated? And finally, for DMD, the fifty percent enrollment, can you clarify whether this includes new patients enrolled into the pivotal, or does it also include the patients from the phase one/two study?

Great. I'll take the DMD parts first, then Steve can talk about DR. For Duchenne, the data we plan to share at MDA will include follow-up on patients previously reported at dose level two out to twelve months, new patients that have not previously been reported in dose level two likely at nine months, and also longer-term data on dose level one patients who will be out further. We don't have a specific count of new patients to disclose now, but we will be enriching the dataset incrementally. Regarding pivotal enrollment: yes, pivotal enrollment includes new patients that have been enrolled since we announced the pivotal study. Some patients dosed in the phase one/two study are eligible to be included as part of the pivotal dataset; recall the pivotal target is n=30.

Hi, Annabel. On diabetic retinopathy and the pivotal plan: fortunately, there's a clear path based on precedent for getting an indication for treatment of diabetic retinopathy using the diabetic retinopathy severity scale, which has been clinically validated to predict bad outcomes. That precedent supports the use of a negative control, such as a sham arm, enabling us to power a study to look for a difference versus control. There isn't identical precedent in Europe, which is one of the reasons we want to work with the EMA and Japan to align on the plan. We think the case gets stronger with more evidence and studies, and we look forward to updating on those discussions with global regulators.

Thank you.

Our next question comes from the line of Brian Skorney with Baird. Brian, you may be on mute.

You're right. All set for me now. Thanks for taking the question, everyone. You've now submitted BLA for Hunter, had discussions going to federal program for DMD and planning a program for diabetic retinopathy. We get a lot of questions about continuity at leadership given the change of guard at HHS and FDA. I don't really know anyone who has more interaction with FDA than you over the last couple months. So just wondering, given recent leadership changes at HHS and FDA, if you could give us a sense as to how up to date you are on discussions with FDA review staff and the Office of Therapeutic Products, and if you're seeing significant change within the review division for these types of products and how much that could potentially impact future gene therapy reviews?

I think our general comment is it's business as usual from our perspective in terms of submissions we're making. We're frequently providing amendments to protocols, INDs, and we're getting questions back and forth. We're not seeing a significant difference either in timing of responses or availability of the review teams. We're encouraged by comments on the rare disease side around accelerated approval from recent leadership and the overall sentiment. To date, we feel we have good connections and previous dialogue with the review team; the review team seems stable from those interactions, and we don't see any change in the risk profile of our pending BLA or ongoing discussions for Duchenne.

And then maybe a follow-up on DMD now that you're about fifty percent enrolled into the 202 pivotal: could you give flavor as to screening? Are you seeing any particular skew by age or characteristics in terms of patients looking to screen? In particular, are you seeing more four to five-year-olds coming in because of earlier data, or are you seeing a broad distribution?

Generally, we see strong interest across the age range. One reason we highlighted nearly half enrollment is to underscore that screening logs and neutralizing antibody testing show a significant number of patients being screened, which reflects strong interest from the patient community and advocacy groups.

I'd say it's a broad distribution. Families across the age range approach options differently. Our differentiation comes into play across ages. Microdystrophin levels we're seeing are clear and differentiating, including in eight and older, and the four to seven and four to five groups are important subsets. Safety is a major differentiator for investigators and families. We believe our proactive immune suppression, transient approach, high purity levels, and overall safety profile are differentiators. So clinicians and families are considering us across the age range. In the one and under to three group, those patients currently have no access to approved gene therapy in the US. We're seeing vector genome copies per cell that are higher than reported by other programs, which gives added confidence for the younger group where there's muscle cell division. In summary, we see strong differentiation that is compelling and supports broad uptake.

Particularly, ninety-five percent of the prevalent market remains untreated, so the market opportunity is large. Focus on next-generation therapies is helping enrollment. We're pushing to go as quickly as possible on all fronts for the BLA submission.

Great. Thank you.

Our next question comes from the line of Paul Choi with Goldman Sachs.

Thank you. Good afternoon and thanks for taking our question. I want to ask on AFFINITY and how you're thinking about post-trial or post-approval commitments and your thoughts on requirements down the road for confirmatory studies or other regulatory commitments. And second, given the data you're seeing to date in the ambulatory population, what's the current appetite to potentially explore 202 in a non-ambulatory population at some point even if it's exploratory? Just your thoughts would be great. Thank you for taking our questions.

Great. In terms of confirmatory studies, we'll discuss in more detail with FDA what's required. In general, we intend to continue to enroll post-pivotal towards the end of completing a confirmatory study as quickly as possible. We'll have further discussions with FDA in our pre-BLA meeting about exact requirements. Regarding non-ambulatory populations, we are strongly considering studies, but not at the expense of going as fast as possible for the ambulatory one-and-older population. It's a consideration given the size of the prevalent market, but we don't want to divert sites from completing the pivotal this year.

Given the excellent microdystrophin levels and functional results we're seeing, it's an interesting dilemma. As Curran said, we'll focus on the pivotal population now, but patient advocacy is increasingly asking about non-ambulatory studies given the logical extension of the results. It's something we'll look at, but not adding acutely to the pivotal.

Our next question comes from the line of Ellie Merl with UBS.

Functional data: specifically, what should we be looking for at the upcoming data update and then thinking longer term both from the pivotal study and then potential confirmatory? What would be differentiating in terms of functional data? And in terms of the pivotal study, how do you plan to analyze some of the functional data? Do you have any plan to do a natural history comparison? And is that something you've discussed with the FDA?

Great. On the near-term functional data, you should expect additional patients treated at dose level two in our phase one/two study with updates at nine and twelve months. We'll report twelve-month data on patients we previously disclosed, and update dose level one patients who will be out further in time. Over the year, I expect most of the seven patients dosed at dose level two to have twelve-month data, but that will be later in the year.

As far as what we'll look at: the usual functional measures — time function tests such as time to stand, ten-meter walk/run, time to climb, and NSAA. Historically NSAA has been seen as less sensitive than time function tests, but in our November update we saw encouraging results on both time function and NSAA. We'll look to confirm those on longer follow-up and expand the sample at dose level two. We'll continue to compare results to matched external natural history controls, which is important because disease trajectory depends on age and baseline severity. We've discussed this approach with the FDA; it was part of the successful end of Phase Two meeting before starting the pivotal.

Thanks.

Our next question comes from the line of Sean McCutcheon with Raymond James.

Hey, guys. One for me on NPDR. Steve, to your point, we've seen some reticence from patients to receive anti-VEGF therapies due to that high burden or frequent injections. You've shown meaningful decreases in vision-threatening events up to twelve months in Altitude at the higher dose, in line or better than the PANORAMA study of faricimab. What do you view as the treatment durability at which we could start to see more utilization in NPDR? And how do you view that as distinct for a gene therapy versus a sustained-release TKI?

That's a great question. Repeated anti-VEGF injections work, but they're too burdensome for patients and doctors to give indefinitely because once you stop the injections, severity often returns. That means you're signing patients up who are currently asymptomatic to get injections the rest of their life, which is a barrier even for longer-acting TKIs. Even injections every six or twelve months still represent repeated injections, and that is a major barrier. That's why we and AbbVie are excited about suprachoroidal in-office one-time injection to address this unmet need. We're excited by the data we showed: an eighty-nine percent reduction in vision-threatening complications at a year in the higher-dose cohort. That outcome was a key driver for AbbVie to accelerate end of Phase Two planning and move toward pivotal this year.

Thank you.

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

Hey, guys. Thanks for taking our questions. Maybe two on DMD. First, how long after completion of enrollment do you think we could see data? Would twelve-week microdystrophin for the primary be enough for a top-line, or would you want to wait longer for other endpoints? Second, what's your expectation around the commercial market dynamics a year or two out when you're closer to approval? Any updated thinking on current supply and addressable market at launch would be great. Thank you.

In terms of market dynamics: we think at least half of the prevalent market will remain available by 2027, which is what we're targeting for potential approval. With a mid-2026 BLA filing, that could lead to a potential approval in early 2027. We're already planning manufacturing for launch; we will have initial commercial-eligible lots starting this fall, and our in-house manufacturing has capacity to support a launch. Assuming we secure a broad label, we plan to be aggressive commercially in 2027 to address a significant portion of the prevalent population.

As for results: the twelve-week time point is our accelerated approval endpoint time point for microdystrophin, so that is a very significant data point. We would certainly disclose that because it's central to an accelerated approval filing and will be a driver for proceeding with a BLA by mid-next year. Safety data will also be available at that time, so it puts us in a good position.

And at the time of filing, we'll have the full phase one/two dose level two cohort past twelve months and a good proportion of pivotal patients with at least nine- to twelve-month functional data to accompany the primary microdystrophin endpoint. We may also update additional safety data in the typical 120-day safety update during review.

Got it. Makes sense. Appreciate the color.

Our next question comes from Yi Chen with H.C. Wainwright.

Thank you for taking my question. Could you comment on Nippon Shinyaku's sales team presence in the US? How many of them will be promoting RGX-121 if it's approved? And do you expect that any sales-related milestone could be triggered within twelve months of commercial launch? Thank you.

I didn't quite hear the first part; could you repeat the beginning of that question? ...The sales force that will service the launch will largely be the same team Nippon Shinyaku has planned for Duchenne and other rare disease launches, and we expect the majority of that team to be applied toward commercialization of RGX-121. Given the BLA filing, we're pointing toward a PDUFA in Q4 of this year and a launch either late this year or early next year if approved. The partnership with Nippon Shinyaku will allow us to move rapidly; they are aligned with site selection for commercial treatment centers. Regarding sales-related milestones: some milestones in our agreement may be achieved in the first or second year of launch. We haven't previously commented on the exact proportion of the total potential milestone pool, but some milestones could be realized in the early years post-launch.

Thank you. I'm showing no further questions in queue at this time. This concludes today's conference call. Thank you for participating. You may now disconnect.