REGENXBIO Inc. Q1 FY2026 Earnings Call

Welcome, everyone, to the REGENXBIO RGX-2026 Top line Pivotal Data Webcast. At this time, I'd like to turn the conference over to Patrick Christmas, Chief Legal Officer of REGENXBIO. Please go ahead.

Good morning, and thank you for joining us today. Earlier this morning, REGENXBIO released pivotal top line data from the AFFINITY DUCHENNE trial of RGX-2026 as well as financial and operating results for the first quarter ended March 31, 2026. The press releases are available on our website at www.regenxbio.com. Today's webcast 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, 2025, and comparable Risk Factors sections 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 14, 2026, 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'll now turn the call to Curran Simpson, President and CEO of REGENXBIO. Curran?

Thank you, Patrick, and good morning, everyone. Thank you for joining us. Earlier this morning, we announced positive top line data from the pivotal trial of RGX-202, our potential best-in-class investigational gene therapy for Duchenne muscular dystrophy. This data is highly meaningful for us and for patients, and we are excited to share it with you today. We have shared very encouraging Phase I/II results for RGX-202 previously. And today, I'm very pleased to have a group of experts with us to reflect on the first Phase III results from our AFFINITY DUCHENNE trial. Our Chief Medical Officer, Dr. Steve Pakola, will present the data before opening the call to Dr. Aravindhan Veerapandiyan, also known by his patients as Dr. Panda, Dr. Carolina Tesi-Rocha and Dr. Diana Castro to share their perspectives. We're also very pleased that Dr. Panda will share videos from his patients treated with RGX-202 to give you a sense of what this positive data looks like for families in a real-world setting. Before jumping into the data, I'll provide a quick recap of the first quarter 2026 earnings, which we also reported this morning. REGENXBIO continues executing against our mission to deliver multiple first and best-in-class gene therapies. As you'll hear today, the positive data and momentum continue for RGX-202. Across the pivotal and confirmatory studies, we have dosed more than 50 patients with line of sight to dosing 60 patients by midyear. Supported by today's updates, we are planning for a potential approval in 2027. In retinal disease, we are on track to dose the first patient in the Phase IIb trial for diabetic retinopathy in the second quarter, which would provide a $100 million milestone payment from our partner, AbbVie. Additionally, preparations continue to report top line data from the subretinal pivotal studies in the fourth quarter. I'm also very pleased to share the partial clinical hold placed on RGX-121 for the treatment of Hunter syndrome has been fully lifted. We recently filed an appeal of the 121 CRL and are continuing to engage the agency regarding a path forward for the program. Overall, I am happy to share that we remain well positioned to have 3 approvals over the next couple of years, including 2 blockbuster opportunities. Turning back to our main event, the RGX-202 pivotal top line results. Today's positive data update is especially meaningful as we look at the impact of this progressive devastating disease. High unmet need remains for Duchenne patients as current options face limitations related to efficacy, safety and access. The untreated Duchenne population continues to grow in the U.S. and globally. Physicians and patients need new next-generation options. Our Duchenne gene therapy program is differentiated from other gene therapies in multiple ways. Our novel construct with the C-terminal domain enables us to deliver a microdystrophin with more key elements of the full-length dystrophin that's missing in boys with Duchenne. With the CT domain, RGX-202 is uniquely designed to better preserve and protect the muscle as demonstrated in preclinical studies. This novel construct, combined with our proactive short-course immune suppression regimen and leading product purity levels allows us to maximize the potential for therapeutic benefit while maintaining an impressive safety profile. I'll now turn the call over to Steve to walk us through the exciting data that reinforces our confidence in RGX-202 as a potential best-in-class therapy for patients. Steve?

Thank you, Curran. Before we dive into the details, let's start with the results. I'm thrilled to share that the pivotal Phase III portion of the AFFINITY DUCHENNE trial of RGX-202 met its primary endpoint with high statistical significance. Patients' functional outcomes exceeded expected disease trajectory across age groups and RGX-202 was well tolerated. Additionally, RGX-202 demonstrated highly statistically significant correlation between microdystrophin expression and functional improvement on NSAA change from baseline and NSAA versus cTAP predicted value. This is a landmark distinction in Duchenne gene therapy, where a correlation of this strength has never been seen. Today's data set includes microdystrophin biomarker data from 30 patients, interim safety from 31 patients and interim 12-month functional data from 9 patients aged 4 and older. I'll note that the microdystrophin data is shown for 30 patients, not 31, as 1 patient refused the 12-week biopsy. Our pivotal study included 31 ambulatory boys aged 1 year or older with any DMD Duchenne mutation except deletions or point mutations in exons 8, 9 or 10. This is a wide enrollment criteria, allowing us to impact both the incident and prevalent populations at potential launch. As we go through the data set, keep in mind that we have treated a very balanced age range of patients in our pivotal study as displayed here. Turning to our microdystrophin data. The primary endpoint of the pivotal study was the proportion of patients with microdystrophin expression above 10% at week 12. The pivotal trial met the primary endpoint with high statistical significance with 93% or 28 of 30 patients exceeding this threshold. Notably, 80% of patients exceeded 40% microdystrophin expression. We saw a 71.1% average microdystrophin expression across all patients and a 41.6% expression in patients aged 8 and older. This is the highest average microdystrophin expression reported for this age group across gene therapy programs. We believe this robust expression supports the potential for improved outcomes. And as you'll see, this is supported by the strong correlation to function. Biomarker data supported consistent robust expression, transduction and sarcolemmal localization of microdystrophin with a high level of vector copies and percent positive fibers. These are among the highest vector copy numbers seen in the field, supporting the potential long-term durability of 202. Turning to interim safety. RGX-202 safety profile is supported by a novel immune suppression regimen designed to proactively mitigate safety events that can occur with high-dose gene therapy. We implemented this short course regimen from the start of the program. Unlike others in the field, it remains unchanged. We believe this targeted proactive approach has been a significant success factor for our program. RGX-202 was well tolerated in line with the Phase I/II data. Of the 31 patients dosed, there were 2 treatment-related SAEs. Both were easily managed and resolved within weeks without sequelae. One was a case of subacute myocarditis, which was reported in an 8-year-old participant. At 33 days after dosing, he presented with mild chest and abdominal pain, normal troponin and mild elevation of high-sensitivity troponin. This event fully resolved without sequelae. The participant's most recent cardiac MRI confirmed no heart muscle fibrosis and no change in ejection fraction. The second case was a case of asymptomatic liver injury reported in a 10-year-old participant and diagnosed via labs 43 days after dosing. This patient's GGT peak elevation was 123 units per liter and his abdominal ultrasound and bilirubin levels were normal. This event also fully resolved without sequelae. The common drug-related adverse events are those typically anticipated with gene therapy and all were considered mild or moderate and resolved without sequelae. Notably, no drug-related thrombocytopenia, myositis or neurotoxicity were reported. We believe this is an impressive safety profile and an important differentiator for the physicians and families making decisions about their gene therapy options. Also supporting our differentiated liver safety profile, mean GGT and total bilirubin, measures of liver injury remain stable and well below upper limit of normal throughout the 12 months. Turning to our exciting interim 12-month functional data. The disease trajectory for Duchenne is well established, allowing use of multiple validated methods with large external data to evaluate our functional outcomes. The primary method in our SAP is propensity score weighting, which mimics a randomization setting. At 12 months, patients are demonstrating functional improvement compared to external controls on NSAA and all timed function tests. Across all four domains, we see a favorable profile for RGX-202 compared with external controls. This remains true for the subset of patients aged 8 and older. These favorable functional outcomes are even more notable in this population where patients are expected to be in the decline phase. At 12 months, caregivers are also reporting improved function on key dimensions of the PODCI that are most relevant to Duchenne. We are pleased to see how these boys are performing in day-to-day activities. These 12-month functional outcomes are incredibly impressive, and we believe are rooted in the novel RGX-202 construct. In a landmark update for Duchenne gene therapy, there is a strong statistically significant correlation between RGX-202 microdystrophin and functional improvement. The correlation is observed for both NSAA change from baseline and change from baseline compared to expected disease trajectory using cTAP. Notably, the correlation coefficient is greater than 0.9 in both analyses. Additionally, correlation between microdystrophin and the timed function tests showed directional trends, and we expect to expand this data set as more patients reach the 1-year mark. This strong correlation supports RGX-202 microdystrophin expression as a surrogate endpoint likely to predict clinical benefit. Now that we've shared these impressive results, let's hear from our expert Duchenne physicians. Dr. Panda, Dr. Tesi Rocha and Dr. Castro. First, thank you for joining us today. And let's start off at a high level and hear what each of your overall impressions are on these top line pivotal data that we presented this morning. And let's start with our investigators and you specifically, Aravindhan, what's your take on these results?

I'm quite impressed by the microdystrophin expression as well as function and most importantly, the functional data of the older boys that are older than 8. I think it's impressive. And as I've shared in the videos of the patients, those are impactful for me. I think it just gives us confidence in RGX-202 in altering the disease progression in these patients.

Thank you for that, Aravindhan. And let's turn to you, Diana, seeing these results for the first time. What's your take?

I think I agree with Dr. Panda. We have been doing this for many, many years. We have heard a lot of other products talking about dystrophin. But my question always is what does dystrophin mean by itself if there is not function associated to the dystrophin level. And I think that this is not only impressive in terms of the amount of dystrophin that we're seeing in these cases, but also that there is correlation with function because at the end, this is what matters for these patients, right, is that how do we prolong their life and how do we keep quality of life as they get older. And the only way we're going to achieve that is it's getting obviously better function as they go.

And so turning to you, Carolina. You've treated patients with 202 in the trial as well. And now that you've seen the top line results, what are your key takeaways?

Well, overall, my impression is that the data is encouraging. The safety profile presented appears favorable, which is critically important in the current DMD gene therapy landscape. And while the functional data set is still limited in terms of the patient number, it's reassuring to see patients showing favorable trajectories, particularly when viewed in the context of the cTAP modeling and historical controls. So that type of comparison is clinically meaningful because it helps frame in a way whether the observed changes are moving in the direction that we all hope as we were in the clinical trial to see beyond the expected disease progression.

Great. So you've all hit on the importance of not just biomarker, but of course, that translating into function. And you've mentioned, Diana, that importance of correlation to really see what does microdystrophin of a particular construct actually mean. So given these results and how you look at it, can you put that in any kind of context as far as the existing unmet needs you see in terms of the patients you treat today and what these results might mean as far as RGX-202 as a potential therapeutic option going forward?

Sure. I think that, like I said, we definitely need to concentrate in function. And what we're seeing in terms of unmet needs, two things. One, we're not treating patients early enough. And I think this is something that you guys are addressing, because we're going to move into newborn screening. And if we're going to end up in that area, we're going to need therapies that are going to address the situation as early as we can. That is one. The other one is that what we have right now, the products we have and what's coming, we talk about the young population 4 and above, but we have to also think how much are we going to get for the patients that are older, the 8- and 10-year-old patients that are obviously getting weaker as the condition progresses. So I think that area is a big area of unmet need and something that we hopefully can address with this type of product if we're getting that function in those older patients as well.

Thank you for that. It's interesting that there is really an unmet need for various reasons across that age range. And how about you, Carolina? Anything to add on unmet needs for your patients and families?

Well, I think that the families remain very interested in gene therapy. But they are becoming increasingly sophisticated on how they think about it. They want to understand not only the potential benefit, but also the durability, safety, immune suppression regimens, eligibility and how the treatment might affect future options. So I think that many families and patients view the gene therapy as an important opportunity, but they are looking for transparent discussion on what is known, what remains uncertain and how we can monitor and mitigate risk. So there are certainly a lot of unmet needs in terms of eligibility. Some programs under investigation have more restrictions in terms of acceptable mutations. Some families face preexisting antibodies to certain AAV vectors that might not make them candidates. So there is an unmet need for those patients who cannot get commercial access to treatment. And certainly, the two groups I would highlight are the very young and the older patients; how these therapies will be useful for them across different age ranges. So I think there are still a lot of unmet needs, but we hope that having more opportunities and different gene therapies with different constructs might help families make decisions in the future.

Aravindhan, what's your view when you think of potential unmet need for your patients as well?

Yes, Steve, I think the therapies that we have in the pipeline as well as those we are using right now are not cures. They're trying to change disease progression. Like Diana was saying, there are older or late ambulatory patients and also younger patients, for whom we don't have a lot of functional data. I think the data presented here today kind of addresses that point. It gives us confidence to use RGX-202 in that population. Also, the correlation between function and microdystrophin expression is unique and reassuring to see that the microdystrophin expressed actually translates into function. I would love to continue to explore that as more patients' data become available, to see how this pans out not just with NSAA but also other functional assessments. I think that is a unique and important result to share.

Great. Thanks, Aravindhan. So as a follow-up to these perspectives, can you say a few words about how you think about the overall benefit-risk profile that you're seeing for RGX-202 when you hear these results?

Sure. As this field becomes more complex, the landscape keeps changing. As physicians and families, we look for therapies that can be stronger, safer and hopefully more predictable. We're already dealing with a complex condition, so for gene therapy we want to feel that we know where we're going. What you're showing is hopefully a more predictable response in terms of safety. For example, liver is one of the biggest complications that we have and one of the causes of more long-term complications, particularly when prednisone is increased to high levels. With the use of different immunosuppressants in this case, hopefully we'll avoid those complications as we treat more patients. Again, it's about finding a therapy that lasts longer, is safer and more predictable across stages of disease.

Thanks, Diana. How about you, Aravindhan? What are you seeing here when you think about the overall benefit-risk profile for RGX-202?

Thanks, Steve. I agree with Diana. From a safety standpoint, I've always felt more confident using a more comprehensive immunosuppressive regimen. Now the field is evolving, and people are using sirolimus as a standard of care, whereas RGX implemented a thoughtful regimen early in the trial. That additional layer of protection against immune-related side effects gives us more confidence to dose more patients with RGX-202, and I see that as a differentiating factor from a safety standpoint.

So last but not least, Carolina, any thoughts on overall benefit-risk considerations having seen these results?

Again, when families decide to pursue gene therapy, there's a lot of potential risk. It's encouraging to see the safety profile presented continue to appear favorable despite the two cases with cardiac and liver abnormalities. This is an element families consider closely. It's positive to see that immunosuppression in this protocol was started from the outset, giving us information about potential safety. Many of us may use different types of immunosuppression initially, not necessarily the same as commercial products. It's reassuring to see a protocol designed to address potential complications and evidence that patients can tolerate this stronger immunosuppression in the trial. That is important for clinicians and families.

Well, that brings us to the end of the panel discussion. So thanks to all of you for your insightful perspectives this morning. Before I turn the call back to Curran, Dr. Panda is actually going to share a video to give us a glimpse into what the data we've shared today looks like for patients he's treated with RGX-202 with videos both in the clinic and in the real world.

I am pleased to share videos from two of my patients who received RGX-202. These first two videos are of a 6-year-old boy. At baseline, he can walk up 4 stairs, placing one foot on each step and touching the handrails. One year later, he performs the task more quickly. At home, he races up a long stairwell with his sibling without using his hands. He makes it clear he's won the race to the top. This same boy at one year post dosing is jumping, clearing both feet off the ground multiple times in a row. He's able to run over leaves and grass in a park and makes his family smile with his dancing. These next videos are of a different boy who was 5 years old at dosing. At baseline, he jumps clearing both feet just off the ground surface. One year after dosing, he jumps higher without placing his hands on his body. The same boy's family recently shared with me how much he enjoys playing on the trampoline. At two years post dosing, he is jumping, rolling and galloping on the trampoline. His parent shared that he played on the trampoline for 16 straight minutes this day. What's impressive about this activity is the muscle strength not only to jump, but to continuously get back up from a bouncy surface. I'm always grateful when the families share their progress and a look at how the changes in muscle strength and endurance are impacting their day-to-day life.

Wow, Dr. Panda, this is incredibly moving. Thank you for sharing these videos, and thank you to all of our esteemed physicians for joining us today. It is so heartwarming to see how well these boys are doing in a real-world setting. It's amazing to see them look happy, strong and having fun with their families one and two years after RGX-202 treatment. It's an incredible reminder of why everyone at REGENXBIO is committed to bringing new next-generation therapies to patients. To sum up what we shared today, RGX-202 demonstrates evidence of positive functional outcomes with an encouraging safety profile supporting potential FDA approval via the accelerated approval pathway in 2027. RGX-202 achieved its primary endpoint with high statistical significance. Interim functional data demonstrate improvement across all functional measures compared to external controls, with highly statistically significant correlation between our novel microdystrophin and function. In our discussions with the FDA, the agency noted whether RGX-202 microdystrophin protein expression can serve as a surrogate endpoint reasonably likely to predict clinical benefit. With our emerging data set, we are demonstrating strong correlation between the two and look forward to discussing this with the FDA at a future meeting. Today's top line data is highly exciting and an encouraging step on our path to deliver RGX-202 as a potential best-in-class therapy for patients and is highly supportive of our plans for potential accelerated approval next year. On behalf of everyone at REGENXBIO, I want to say thank you to the patients, families, physicians, study sites and advocates who have partnered with us on this mission.

Now we'll open the line for Q&A. Our first question comes from the line of Judah Frommer from Morgan Stanley.

Thanks for the presentation today, all the incremental data and for providing us with this panel. It was really helpful. Maybe one just on the liver SAE. GGT of 123 didn't look all that high. I think you said it was two times upper bound by one reviewer. So maybe just some color on the adjudication of that SAE. And then I have a separate follow-up.

Great. Thanks, Judah. Good to hear from you. I'll start that question off with Steve. He can comment and work with the panel if needed.

Sure. Thanks for the question, Judah. Yes, so out of 31 patients, we had the one liver injury. We had no other cases of liver injury. Yes, as you mentioned, it wasn't a particularly high liver enzyme elevation. But I think in this field, there's a desire to really stay on top of these patients. And in a clinical trial, there's a lot of frequent assessments. So as far as the adjudication, the way SAEs work is whether you meet any of the criteria. And one of the criteria is hospitalization. So there's various reasons why a patient would be hospitalized. Sometimes it can even be for administrative reasons depending on availability of outpatient infusion, for example. So in this case, this patient was one of your patients, Carolina. Since we have the benefit of you here, I'll turn it over to you as well to give your perspective on how the patient did and how the patient is doing and also circumstances around determination that it was an SAE.

Yes. Thank you, Steve. That is absolutely right. The reason why this was determined to be an SAE was exactly because of administrative issues in terms of the inability to use the infusion center over the weekend. The complication happened on a Friday. So we decided to do pulse Solu-Medrol, and we were not able to do that in the outpatient infusion center. So that was the only reason. The patient was always asymptomatic. This was just a laboratory finding with abnormalities as they were mentioned before. GLDH was also elevated. So we already had plans to pulse this patient with Solu-Medrol. However, based on the GGT, AST and ALT elevation that were trending up despite CK trending down, indicating the increase in liver enzymes were not attributable to increase in CK, we were motivated to treat even before getting GLDH from the central lab. These results came back around the same time and showed a level of five times the upper limit of normal for GLDH. Consequently, we gave the patient five pulses of Solu-Medrol at 30 milligrams per kilogram, which he tolerated well. We also ran other tests to rule out other potential causes for the enzyme elevation. Viral tests came back negative as well as other metabolic labs.

Thanks, Carolina. I'll also add that not only were there no other liver injury cases in the other patients, but even looking at a very granular level at the liver enzymes in all the patients, even with this patient included on a mean basis, there's no suggestion of liver injury subclinically. So this really does round out a very nice picture for liver safety as a differentiator from existing therapy where there's a recognized 40% rate of liver injury. So we're very happy with these safety findings.

Okay. Great. And then just on the regulatory path from here. In the press release, you mentioned recent discussions with FDA and recommendation for a randomized controlled trial, but it seems like there's openness to interpretation of biomarker correlation to functional benefit. So anything you could elaborate on how these nine patients and how many additional patients will need to potentially avoid a randomized controlled trial? And then if I could just sneak one more in for the panel. Just curious on that comment about sophistication of patients and families. How many do you sense are waiting for next-gen therapies beyond gene therapy? Or is there still a desire to get therapy to patients as quickly as possible?

Thanks, Judah. I'll take the first one, and then I'll send over to Steve for the patient perspective. I think on the FDA interactions we've had, none of them have really been in a situation where we've actually reviewed this data. Of course, we just unblinded it recently. I think the magnitude of effect we're seeing here is directly applicable to the accelerated approval pathway. The concern with the review team is more bias that could be introduced using external control strategies. But when you consider that and the experts we've worked with, the bias that would exist is dramatically overcome by the magnitude of effect we're seeing in functional benefit. There's no specific request from FDA to show a specified number of patients for functional data as part of accelerated approval. What was specifically requested was to show the correlation, and given the strength of the correlation that we've shown, I think we have what we need to demonstrate that. It's the first time any gene therapy study has shown this level of correlation between the surrogate biomarker and functional outcome. So I think our data will be very strong in supporting that. Now I'll kick it over to Steve.

Yes, it's a good point that Duchenne patient families are often very sophisticated. For example, some families are even raising their comfort level with product purity over 80% full capsids, which is pretty sophisticated. Diana, given your experience treating these patients and families, could you say a few more words about how this impacts your conversations with families about treatments in the pipeline, and how these attributes give families greater comfort?

Of course. I have the privilege of running a nonprofit clinic, so we see patients with and without insurance. It's interesting how much families are learning about these therapies. Social media and families talking to each other contribute. They do their own research, and it's important for us to be prepared to answer their questions. One impactful point to families is information about capsids and purity; that makes a big difference because families are already taking a risk. They want to understand whether the risk will translate into more microdystrophin and, hopefully, more function. It's never an easy decision for families, but with more predictable responses and better safety profiles we can change the decision-making in a positive way.

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

I wanted to touch base on timing of FDA engagement. How do you think about timing of the engagement, timing of filing, maintaining a sense of urgency around the unmet need to support accelerated approval?

Certainly, the sense of urgency is extremely high. Right now, the treatment level for the approved gene therapy is lower than the incidence level for new patients that need treatment. We want to go as quickly as we can with filing. We have options to file as a rolling BLA or as a full BLA depending on timing. Our timing on further discussions with FDA will account for the agency's leadership transition, which is significant. We do want to let that settle in. We expect new leadership may have a mandate on rare disease flexibility. With that environment, we're in great shape with our data to push for accelerated approval. We are aiming for a potential approval in 2027. That would mean filing sometime in the early first half of 2027 to achieve that, and we're on track to do so.

Great. As a quick follow-up, could you give me a sense of potential outcomes of that engagement? If the FDA recommends a randomized controlled trial, how would you think about filing and potential changes to the confirmatory trial?

That's a great question. Guidance over the last couple of years has shown that if an accelerated approval requires starting an RCT from scratch, completion timelines could push approvals out to 2030. I don't think the Duchenne community would accept a four-year delay. Our data are clear and significantly different from natural history analyses. The discussion will be collaborative. If the confirmatory study requires pivoting to an RCT to satisfy accelerated approval, we would consider that. It might need to be run ex-U.S. because it's challenging to run such a study in the U.S. That will be a key part of our discussion with FDA in the second half of this year.

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

Congrats on the progress across the pipeline. Two questions on 202. First, how do you expect the picture of functional benefit to evolve as you move toward the full 60-patient data set? Anything in terms of balance of patient age or other factors that could differ from the nine patients you shared? And when might we see this data?

Great question. For the first 30 in our pivotal, we've seen a pretty even distribution of patients in the 1 to 4, 4 to 7 and 8 and older groups. I'll let Steve comment on enrollment for the confirmatory study and additional data updates.

Alec, thanks for the question. We've shown nine patients with 12-month functional data that were available by the time of top line analysis. Five of those nine were from Phase I/II carried into the pivotal cohort. We added four additional subjects. Importantly, the demographics of these nine patients match very well with the overall data set, which gives us confidence that the results are not driven by a fluke of patient selection. We will continue to accrue more data, and we expect the broader data set to support and replicate these findings.

Okay. And then maybe one quick follow-up. Do you expect the review team or the framing of the conversations to change with recent leadership changes at FDA?

The review team has been consistent over the years regardless of leadership. Most prior meetings did not have this data on the table. Once we have discussions where this data is available, I expect a more productive, data-driven exchange with the review team. If you read the accelerated approval regulation, the elements we are providing check those boxes, so we expect a substantive conversation based on data rather than hypotheticals.

Our next question comes from Annabel Samimy from Stifel.

On the correlation analysis, if you're filing by the first half of 2027, do you have a sense of how many patients will have completed the 12-month functional assessment? Could you have a very significant data set to provide on your initial BLA?

We would expect to have at least 50 patients for safety based on enrollment in the confirmatory study. For function, the 4-and-older patients provide most of the assessments. I would give a range of 15 to 20 patients having completed their 12-month time point by an early 2027 filing. That should provide meaningful functional data alongside a robust safety database.

That's helpful. As another follow-up, some programs have demonstrated microdystrophin increasing over time. For patients who did not show greater than 10% at week 12, have you measured expression over time? Could they potentially exceed that threshold later?

We only have the one biopsy at 12 weeks in the protocol. We don't have additional biopsies for later time points. Historically, some data suggests expression can increase over time, but importantly, 80% of patients treated had greater than 40% microdystrophin at week 12. So even if some patients increase later, the vast majority are already well beyond key thresholds.

That's exactly right. We limit biopsies to minimize burden on families. Three months is a conservative measurement point. The most important questions are translation to function and the correlation with microdystrophin, and we're pleased to have evidence on both fronts.

Our next question comes from Luca Issi from RBC Capital Markets. Our next question comes from Brian Skorney, Robert W. Baird.

Congrats on the data. What would the hurdles be to running an entirely separate randomized controlled study, separate from your ongoing confirmatory study? Having an RCT could address potential issues with regulators, payers and stakeholders. Do you think this would be an IRB ethics issue? And to the investigators, does this data break equipoise for running an RCT?

Running an RCT with gene therapy is highly challenging. Patients typically know whether they've received gene therapy based on administration, making blinding difficult. There are countries where standard-of-care gene therapy doesn't exist, and those could be logical places to run an RCT. It is more likely to be feasible ex-U.S. than in the U.S. due to those logistical and ethical considerations. Steve, perhaps you can address this with the panel.

Carolina, Brian asked about equipoise given these results and the feasibility of an RCT, at least from a U.S. perspective. Could you comment?

I agree with prior comments that access is an issue globally. When a commercial gene therapy is available in the U.S., it becomes very challenging to run a randomized placebo control here. If we do pursue an RCT, international sites will be important. Many countries have strong groups that have participated in other clinical trials and could support such a study. It is doable and could provide access to patients who otherwise travel to participate in trials.

Our next question comes from Sean McCutcheon of Raymond James.

Can you speak to how many patients from this analysis were previously included in Phase I/II and what's the trend in microdystrophin expression and functional outcomes for newly disclosed patients? And for the docs on the panel: please comment on your comfort with the prophylaxis regimen and whether you see eculizumab providing additional safety benefit relative to other microdystrophin gene therapy programs?

Sean, thanks. Steve will address the Phase I/II carryover question. For the prophylaxis regimen and eculizumab, we'll defer to the investigators to comment on real-world experience in the trial.

Sean, five of the nine patients with 12-month functional data were from Phase I/II and carried forward into the pivotal cohort. We added four additional subjects for this data set. The added patients also show high magnitude of effect compared with external controls. Regarding the immunosuppressive regimen, we implemented this targeted regimen from the start and haven't had to change it. We believe it contributes to the favorable safety profile. Panda and Carolina, could you comment on your experience with this regimen and eculizumab specifically?

From an immunosuppressive standpoint, especially with eculizumab, we haven't seen complement-mediated issues like TMA. That likely reflects the protective effect of eculizumab plus immunosuppression. Initially, I had reservations about added side effects from multiple agents, but we have dosed several patients with eculizumab and sirolimus and it's been generally well tolerated. This gives us confidence to use the immunosuppressive regimen to prevent immune-related side effects.

I fully agree with Dr. Panda. Initially I had concerns, but the experience has been positive for both my team and families handling this regimen and the extra visits for eculizumab infusions. Overall, it's encouraging and supports continued use.

Our next question comes from Daniil Gataulin of Chardan.

Congrats on the progress. For microdystrophin expression, what is the age of the participant who did not achieve the 10% threshold, and were there any underlying characteristics that may have prevented achievement?

Thanks, Daniil. I'll let Steve answer.

This patient was in the 4 to 7 age range. There wasn't anything demographically unique about this patient. Occasionally a patient or family may decline a biopsy based on their experience with the baseline biopsy. We obtained baseline biopsies for all participants, and this single missing week-12 biopsy was the reason the N for expression is 30 rather than 31. Overall, the results across the 30 patients are very impressive.

Our next question is from Paul Choi at Goldman Sachs.

Can you hear me now? My first question is for the panelists. Regarding the correlation presented between microdystrophin and functional results, the data seem clustered in the middle. Do you feel like 40% is the minimum threshold likely to result in functional improvement? And second, regarding the FDA, will you present any additional one-year data cuts over the course of 2026?

Thanks, Paul. On the FDA conversation, we would expect additional functional data updates as more patients reach 12 months. We don't have a specific date but would anticipate an update possibly in the fall of 2026.

On the correlation and clustering: the clustering is actually encouraging because it shows the majority of patients have strong expression levels that may translate to functional benefit. I'll turn to Dr. Panda, since many of these patients were treated by him. How do you interpret the correlation data and whether a specific cutoff like 40% is necessary for benefit?

I was impressed and pleasantly surprised to see a direct correlation. Given the small N, it's hard to define a strict cutoff like 40%. Historically, 10% has been used because we've seen functional improvements at that level. I wouldn't conclude from this analysis that you must have 40% or 50% microdystrophin to achieve function. The data suggest benefit across a range of expression levels.

Our final question will come from Yi Chen from H.C. Wainwright.

Could you comment on whether the FDA has indicated how many patients would be needed for the safety profile of the drug if accelerated approval is being pursued? Particularly, is there such a requirement for patients less than four years old?

Good to hear from you. The pivotal protocol prespecified 30 patients and that design was reviewed by FDA without comment. We feel from a safety standpoint that this provides what is needed to support a filing. By the time of filing we'll have more than that—closer to 50—based on enrollment rates in the confirmatory study. We believe this should be an adequate safety sample size, particularly given the low frequency of SAEs observed to date. Regarding patients under four years old, the pivotal study included ambulatory boys aged one year or older under broad enrollment criteria. Our approach across age groups is part of the dataset we will present to regulators.

That concludes our question-and-answer session. As a reminder, a webcast replay will be made available on the REGENXBIO corporate website. Thank you for joining.