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DATE

May 14, 2026

CALL PARTICIPANTS

• President and Chief Executive Officer — Curran Simpson
• Chief Medical Officer — Steve Pakola
• Chief Financial Officer — Patrick Christmas
• Investigator and Panelist — Aravindhan Veerapandiyan
• Investigator and Panelist — Diana Castro
• Investigator and Panelist — Carolina Tesi Rocha

TAKEAWAYS

• Pivotal RGX-202 Phase III Data -- The pivotal portion of the AFFINITY DUCHENNE trial met its primary endpoint with high statistical significance; 93% of patients (28/30) achieved above 10% microdystrophin expression at 12 weeks.
• High Biomarker Response -- 80% of patients achieved microdystrophin expression above 40%; mean microdystrophin expression was 71.1% across all patients and 41.6% in patients 8 years and older.
• Functional Efficacy -- Interim 12-month data for 9 patients aged 4 and older demonstrated functional improvement compared to external controls across NSAA and all timed function tests.
• Unique Correlation -- There was a statistically significant correlation between microdystrophin expression and functional outcomes, with correlation coefficients greater than 0.9 for both NSAA change from baseline and cTAP-predicted measures, a distinction described as having "never been seen" in Duchenne gene therapy.
• Safety Profile -- RGX-202 was well tolerated; of 31 dosed patients, there were 2 treatment-related serious adverse events, both non-severe and fully resolved without sequelae (one subacute myocarditis, one asymptomatic liver injury).
• Liver Safety -- Mean GGT and total bilirubin remained stable and under the upper limit of normal through 12 months, with no clinical or subclinical evidence of liver injury in the dataset.
• Patient Population -- Enrollment in the pivotal study included a broad range: 31 ambulatory boys aged 1 year or older, with any Duchenne mutation except deletions or point mutations in exons 8, 9, or 10.
• Regulatory Progress -- The company anticipates a potential regulatory filing aiming for accelerated approval in 2027, with a safety database expected to exceed 50 patients at filing.
• Pipeline and Milestones -- First dosing for the Phase IIb diabetic retinopathy trial is anticipated in the second quarter, which would trigger a $100 million milestone payment from AbbVie; topline data from subretinal pivotal studies in retinal disease are expected in the fourth quarter.
• Regulatory Hold Update -- The partial clinical hold on RGX-121 was fully lifted; an appeal of the complete response letter (CRL) was recently filed, and regulatory engagement is ongoing.
• Immunosuppression Regimen -- The protocol incorporated a short-course immunosuppression regimen from inception and has not required modification throughout the program.
• Enrollment Progress -- Over 50 patients have been dosed with line of sight to 60 by midyear; demographics for patients with 12-month data match the broader study population.

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RISKS

• The call explicitly identified challenges with the requirement for a randomized controlled trial as "untenable" for timely approval, emphasizing that such a requirement could delay approval of new gene therapies until 2030.

SUMMARY

REGENXBIO (RGNX 1.75%) reported pivotal RGX-202 trial data showing an unprecedented correlation between microdystrophin expression and functional clinical outcomes in Duchenne muscular dystrophy. The interim efficacy results included measurable improvements on NSAA and timed function tests in patients 4 years and older, supported by highly favorable biomarker and safety readouts. A broad eligibility criterion enabled recruitment of a demographically diverse patient population, supporting both incident and prevalent market potential.

• Management indicated that FDA discussions will focus on the demonstrated correlation between the biomarker and function as grounds for accelerated approval, with no minimum number of functional data points specified by FDA to date.
• Panel feedback underscored the program’s differentiated safety profile, with no cases of drug-related thrombocytopenia, myositis, or neurotoxicity reported, and a consistent immunosuppressive approach supporting tolerability.
• Program updates included the lifting of the RGX-121 clinical hold and anticipated achievement of a $100 million commercial milestone from the AbbVie collaboration following the first dosing in diabetic retinopathy.
• Current regulatory strategy allows for flexibility, including plans for a confirmatory or potentially ex-U.S. randomized trial, as required by evolving regulatory feedback.
• Patient and family decision-making is characterized by an increasing focus on treatment durability, product purity, and comprehensive safety data, influencing market readiness for both current and next-generation gene therapies.

INDUSTRY GLOSSARY

• Microdystrophin: A truncated yet functional version of the dystrophin protein, engineered for gene therapy to address deficiencies in Duchenne muscular dystrophy.
• NSAA: North Star Ambulatory Assessment; a standardized, validated scale used to measure physical function in ambulatory Duchenne patients.
• cTAP: Collaborative Trajectory Analysis Project; a statistical approach using external natural history control data to benchmark clinical outcomes in rare diseases.
• GGT: Gamma-glutamyl transferase; an enzyme measured as a biomarker for liver injury or dysfunction.
• CRL: Complete Response Letter; FDA communication that details deficiencies that preclude approval of a drug application.

Full Conference Call Transcript

Patrick Christmas: 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?

Curran Simpson: 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?

Steve Pakola: 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?

Aravindhan Veerapandiyan: 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.

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

Diana Castro: 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 means by itself if there is not function associated to the dystrophy 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 it 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.

Steve Pakola: 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?

Carolina Tesi Rocha: Well, overall, my impression is that the data, it's encouraging. The safety profile presented appears favorable, which is critically important, right, 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.

Steve Pakola: 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?

Diana Castro: Sure; I think that, like I said, we definitely need to concentrate in function. And what is -- what we're seeing unmet needs, two things. One, we're not treating patients early enough. And I think this is something that you guys are addressing, which -- 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 progress. So I think that, that area, it's 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.

Steve Pakola: 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?

Carolina Tesi Rocha: Well, I think that the families are -- remain very interested in the gene therapy, right? But there is increasingly -- 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 like certainly a lot of unmet needs in terms of eligibility.

So there are some programs that are currently in investigation, and they have more cuts in terms of what could be acceptable in terms of the mutations that the patients have. Some of the families deal with positivity of some of the AAV vectors that might not make them candidates. So is the unmet need for those patients that cannot get commercial access to treatment. And certainly, the two I would say, age groups, those that are very young and those that are very old, how these therapies will be useful for them in these different type of age ranges.

So I think that there are still a lot of unmet needs, but we hope that at least having more opportunities and different gene therapies with different constructs might help them make their decision in the future.

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

Aravindhan Veerapandiyan: Yes, Steve, I think the therapies that we have in the pipeline as well as that we are using right now, I mean we used to say that none of them were cure. They're trying to change the disease progression. And like Diana was saying, there are those older patients or late ambulatory patients and also younger patients, which we don't have a lot of data available to show their function. And I think the data that's presented here today kind of addresses that point. So it gives us confidence to use RGX-202 in that population.

And also second, the -- with Diana's comment on correlation between the function and the microdystrophin expression, which is unique, and it was reassuring to see that the microdystrophin that is being expressed actually translates into function. And I would love to continue to explore that as we get into more -- looking at more patients data from the trial to see how this pans out, not just with the North Star Ambulatory Assessment score, but also with the other functional assessments. And I think that is a unique analysis and unique results that we should share to show the impact of this microdystrophin construct.

Steve Pakola: 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?

Diana Castro: Sure. I mean as this field becomes more complex, this landscape keeps changing. I think as physicians and families, patients, we're looking for something that -- therapies that can be stronger, therapies that can be safer and hopefully more predictable for the patients. We already are dealing with a complex condition. So when it comes to how to deal with a therapy like gene therapy, we, as physicians, we want to feel that we know where we're going. So what you're showing is hopefully a more predictable response in terms of safety. For example, liver.

Liver is one of the biggest complications that we have and one of the causes of more really long-term complications in terms of gaining weight and so on with the fact that we have to increase prednisone to really high levels. So with the use of different immunosuppressors in this case, with your therapy, hopefully, we're going to avoid those complications as we treat more patients. But again, I think it's just about how do we find a therapy that it will last longer, that will stay -- that will be more safe and also more predictable for different stages of the disease.

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

Aravindhan Veerapandiyan: No. Thanks, Steve. I agree with Diana. I know the -- from a safety standpoint, like I've always said, I feel more confident using more comprehensive immunosuppressive regimen. Now as you know, now the field is evolving and people are using sirolimus as a standard of care, whereas RGX was thoughtful that we implemented this early on as part of the trial. And I think that, that additional layer of protectiveness against these -- to prevent these immune-related side effects, I think that gives us a little bit more confidence to dose more patients with RGX-202. And I think that is definitely a differentiating factor that I would say from a safety standpoint.

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

Carolina Tesi Rocha: Right. So again, they know that when they make the decision to get gene therapy, there's a lot of potential risk. And again, it's good and encouraging to see the safety profile presented continues to appear favorable despite these 2 cases that presented with both the cardiac and liver toxicity complication. I think that this is one of the elements that the families are looking at. Nowadays, we have for the commercial use of gene therapy, the add-on -- the potential add-on of more immunosuppression, but seeing that immunosuppression in this particular protocol was started from the get-go. So then we have the information about the potential safety, right?

So many of us, we could be using different type of immunosuppression initially not suggested by the commercial products and currently under investigation. But it's nice for me to see as a clinician that here in the protocol, we design it in a way that makes sense for the potential complications. And we are also during the clinical trial, not only see the safety profile that appears favorably, but how our patients are able to tolerate this stronger immunosuppression that pertains to the particular gene therapy trial. So I think that, that is -- it's very important for me as a clinician, but I think it's very important for the families, too.

Steve Pakola: 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.

Aravindhan Veerapandiyan: 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 1 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 1 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 2 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.

Curran Simpson: 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 1 and 2 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.

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

Judah Frommer: 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 2x upper bound by one reviewer. So maybe just some color on the adjudication of that SAE. And then I have a separate follow-up.

Curran Simpson: 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.

Steve Pakola: 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 -- and actually, in this case, this patient was one of your patients, Carolina. So 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.

Carolina Tesi Rocha: 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 of us to use the infusion center over the weekend. The complication happened on a Friday. And 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 laboratory finding with abnormalities as they were mentioned before. GLDH was also elevated. So we already have plans to pulse this patient with Solu-Medrol.

However, based on the GGT, AST and ALT elevation that were not -- they were trending up despite the CK trending down, indicating the increase in the liver enzymes were not attributable to the increase in CK. So that is what motivated us to think about the Solu-Medrol even before getting the GLDH from the central lab. But these results came back around the same time and showing a level of 5x of the upper limit of normal. So consequently, we decided to give the patients 5 pulses of Solu-Medrol at the 30 milligrams per kilogram, which he tolerated well.

And we also have the opportunity to run other tests to rule out other potential reasons for him to have this elevation on the liver enzymes. And both viral tests came back negative as well as other metabolic laboratories that were done at the time.

Steve Pakola: 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, no suggestion at all 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.

Judah Frommer: 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 9 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 kind of get therapy to patients as quickly as possible?

Curran Simpson: 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 that 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 that we're seeing here is directly applicable to the accelerated approval pathway. So the concern with the review team is more bias that could be introduced using external control strategies. But I think when you consider that and the experts that 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 x number of patients functional data as part of AA. But 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 show that. I think 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 is going to be very strong in supporting that. Now I'll kick it over to Steve.

Steve Pakola: Sure. Yes, it's a good point that the Duchenne patient families are often very sophisticated. And we, for example, hear feedback from patient advocacy that some families are even raising their comfort level with the product purity with over 80% full capsids, which is pretty sophisticated for a patient family. And Diana, raising that aspect that you obviously have a lot of experience treating these patients and families. You're raising this aspect. Can you say a few more words about that and how that really impacts how you talk to the patients families about different treatments and treatments in the pipeline that can give greater comfort to these families.

Diana Castro: Of course. Good morning, everybody. I have the privilege of -- we have a nonprofit clinic. So we take people with insurance, without insurance, private and so on. And it's very interesting how it really people are learning so much about these therapies. And I think, obviously, social media, right? Families talk to each other. They are doing their own research. And it's important for us also to be prepared to answer their questions. And I think when I start mentioning things about as we learn -- because we don't know everything. I don't know everything for sure.

And as we learn, I think one of the more impactful points to me when I heard about the capsids and when you transmit that knowledge to the families, I think that makes a big difference because they are already taking a risk. They're already making a big decision in their families with their sons. But now they are hearing, well, we're making this risks, but then hopefully, we're going to make -- we're going to get more medication. Hopefully, that's going to translate into more microdystrophin and hopefully into more functions. So it's never going to be an easy decision for these families.

But we're making them, like I was saying before, more predictable, hopefully, and with a better safety profile, we are playing in a completely different -- it's a completely different game, I will say. So it's just -- the knowledge is coming up. We have to keep learning. We have to keep being open about everything that is coming, but knowing that families are more educated right now and they know what's going on.

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

Mani Foroohar: I wanted to touch base on timing of FDA engagement. I know it's something we've talked about on and off. We talked about in the call in light of some commentary that you made with a reporter at Stat News, an article that came out. 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?

Curran Simpson: Well, 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. So I think that is a really important factor in our timeline. We want to go as quickly as we can with filing. We have options to file as a rolling BLA or as the full BLA depending on when we submit. I think our timing on further discussions with FDA, we do want to -- obviously, FDA is going through a leadership transition, which is significant. We do want to let that settle in.

We expect that the new leadership will, I hope, have a mandate on rare disease flexibility. I think those are the indications that we're hearing that will be, I think, more uniformly adopted. And with that environment, we're in great shape with our data to push for accelerated approval. So I think what we're absolutely pinning on is the ability to have an approval in 2027. That would mean we have to file sometime in the first half -- early first half of 2027 to achieve that, and we're on track to do so.

Mani Foroohar: Great. And as a quick follow-up, could you give me a sense of where we are in terms of the potential outcomes of that engagement? Obviously, you have a confirmatory study ongoing, exactly what the FDA might want post the conversation is not exactly -- is exactly to have the meeting with them. Talk about the range of outcomes of that upcoming discussion, how to think about the path forward to accelerated approval? Any potential changes to the confirmatory trial that might be needed depending upon the FDA's attitude towards the necessity for a randomized trial?

Curran Simpson: Yes. I think that's a great question. And I think on the subject of a randomized trial, given that there has been guidance over the last couple of years from FDA that the accelerated approval pathway is open to start an RCT study from scratch, which we see some entrants doing that, even the commercial product doing that, you wouldn't see an approval based on timeline estimates until 2030. So I can't imagine an environment where the Duchenne community is willing to wait 4 years for an approval of an RCT study base. And so what I think will help us -- will help -- the unmet need will be clear.

Our data is really clear and very significantly different from what we see with natural history analyses that we're doing. And I think the discussion on our end will be very flexible. If the confirmatory study were nearly completed or needs to shift to an RCT study as part of accelerated approval, we would consider that. I think that's something that we'd have to determine if that has to be run ex U.S. because I think it's challenging to run such a study in the U.S. But that, I think, is the heart of the conversation that we'll have with FDA second half of this year.

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

Alec Stranahan: Congrats on the progress you're making across the pipeline. Two questions from me, both on 202. I guess, first, how do you expect the picture of functional benefit to evolve as you move towards the full 60-patient data set? Anything in terms of balance of patient age or other factors that could differ from the 9 patients you shared? And when might we see this data?

Curran Simpson: Great question. I think on the age distribution 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. And I'll let Steve comment on enrollment for the confirmatory study and what we're thinking about in terms of additional data updates.

Steve Pakola: Yes. Alec, thanks for the questions. Yes, it's a great point you raised that we've shown 9 patients worth of data that was based on everything we could get in there as far as how many patients in the 4 and older age group had reached the 12-month time point by the time of the top line data coming in. So an issue is how much confidence do we have going forward of that replicating when we have more patients. We didn't have time or to have slides that really break down demographics of the different patients. But we have had time to look at that.

And fortunately, the demographics of these 9 patients match very well with the overall data set. So that gives us a lot of confidence as we go forward that the very impressive results we're seeing here are not driven by any fluke of the type of patients that are in this 9 out of 31.

Alec Stranahan: Okay. And then maybe just one quick follow-up to a question that was asked earlier, but maybe I'll ask it in a slightly different way. I guess, do you expect the review team or the framing of the conversations you're having, like did this change at all once the FDA heads turned over a couple of years ago? And do you expect that to change given the recent departures as well?

Curran Simpson: That's a great question. I think that the review team has been consistent over the years regardless of leadership that was in place at the time of the different meetings. But I think, again, I'd caution that the meetings that we've had other than our end of Phase II, where we had some limited data to share have all been devoid of the data that we're showing you today. And I think once we have that conversation with FDA where this data is on the table for discussion, I think it will be more productive on both ends to look at what we've got, to look at the magnitude of effect that we're seeing.

As I've said recently, I think we have everything -- if you read the accelerated approval regulation, all of the elements that we are providing check those boxes. So I think that's where we're looking to meet with the review team and actually have a data-driven discussion rather than hypothetical of just general assumptions.

Operator: Our next question is from Annabel Samimy from Stifel.

Annabel Samimy: So on the question of the correlation analysis, if you're filing by the first half of '27, do you have a sense of how many patients will have completed the 12-month functional assessment? And could you actually have a very, very significant data set to provide to them on your initial BLA? So that's the first question. I have some follow-up.

Curran Simpson: Yes. I think the expectation would be early '27 filing, we would have, importantly, on safety, at least 50 patients available based on the enrollment rate that we had for the confirmatory study. So on the safety database, significantly more than what we're showing here, which is great. On function, if you look at the proportion of patients in these age categories, as I said, fairly evenly balanced. If you think about functional assessments, then it's the 4 and olders that contribute most to the assays that we're describing. And we would have -- I would just give a range, 15 to 20 of them through their 12-month time point at that point. Is that helpful?

Annabel Samimy: Yes, that's helpful. That's great. And just as another separate follow-up. So in terms of the microdystrophin expression, I know some have demonstrated microdystrophin expression increasing over time. Of the patients that did not show greater than 10%, is there -- have you been measuring their microdystrophin expression over time? And do you think there is an opportunity for them to actually have that sufficient dystrophin expression post that 3-month time point of measurement. I'm just curious how these patients might evolve.

Curran Simpson: Yes, we don't -- I think the data you're referring to was data early in the Pfizer study where at 12 months, there definitely was an increase. We only have the one biopsy that's taken at 12 weeks to measure microdystrophin. We don't have additional biopsies in the protocol for measurement at a later time point. But I think it's important in the data set to note that 80% of the patients treated had greater than 40% microdystrophin. So if there's a threshold effect, I think we're well beyond that for the vast majority of patients on microdystrophin. So I think we're really pleased with that data set. Steve, I don't know if you want to follow on with that.

Steve Pakola: Yes, that's exactly right. We have in the trial open biopsy to really have the most robust ability to assess. But that also means you really want to limit how many of these you do for these patients and the families to go through the biopsy. And we're really helped by the data that you've mentioned, Annabel, that we know historically, if anything, it's going to go up. So I think 3 months is a conservative estimate. Of course, we don't know for sure with any given program, but this is really impressive for where there's the most data. And of course, the biggest thing is, is this translating to functional benefit?

And can we even show a correlation with this data. So we're really happy to have ticked both those key boxes.

Operator: Our next question is from Luca Issi from RBC Capital Markets. Let's move on. Our next question comes from Brian Skorney, Robert W. Baird.

Brian Skorney: Congrats on the data. My question is, what would the hurdles be to running an entirely separate randomized controlled study, even separate from your ongoing confirmatory study, just seems like having an RCT running would address a lot of potential issues down the road, whether it be FDA recommendation for accelerated approval based on the recommendation for an RCT to establishing ex U.S. approvals to giving payers and stakeholders better data to work with. It seems like there isn't an available gene therapy across most of the world. So it seems like having a placebo arm could be something viable. Do you think this would be an IRB ethics issue? And in that vein of questioning for Dr.

Panda, Rocha and Castro, do you think this data breaks the equipoise for running RCT?

Curran Simpson: Thanks, Brian. That's a great question. I think in general, running RCT-based study with gene therapy is highly challenging, and I'll let the experts comment more on that because I think very quickly, patients typically know whether they've gotten a gene therapy or not based on the administration of gene therapy. So being able to fully blind a study of that type is a challenge. I do agree that there are countries where standard of care does not exist in terms of an available gene therapy. And those are logical places that we would consider as we are considering a study for ex U.S. licensure of that nature.

So yes, I think it can be done more likely ex U.S. than within the U.S. But Steve, maybe you could address this with the panel.

Steve Pakola: Sure. Carolina, why don't we pass this on to you the question of equipoise given these results, and at least from a U.S. perspective, how you think of an RCT.

Carolina Tesi Rocha: Yes. I agree with the comments that access is an issue. And when we look at this globally, it's a problem for other countries that don't have the possibilities. But that also opens the opportunities for us in this particular case with when we have an already approved commercial drug, it becomes very challenging to be able to do a randomized placebo control in the U.S. So I agree with others that if we do this, it will have to be counting on international sites. And certainly, there are like different places in the world that have very good groups that have participated in other clinical trials. So I think it's doable.

And it will also allow access to these patients that sometimes they have to travel internationally to our sites to be able to participate. So I would like to see that.

Operator: Our next question comes from Sean McCutcheon of Raymond James.

Sean McCutcheon: Can you speak to the number of patients from this analysis that were previously included in the Phase I/II assessments and what you're seeing on the trend in both microdystrophin expression and particularly in functional outcomes for the newly disclosed patients? And then maybe one for the docs on the panel. If you could please speak to your comfort with the prophylaxis regimen as well as maybe speak to whether you see the added eculizumab as providing additional safety benefit relative to your experience with other microdystrophin gene therapy programs?

Curran Simpson: Sean, thank you for the question. I'll let Steve comment on the study design and the number of patients from Phase I/II.

Steve Pakola: Sure. Thanks, Sean. So we have the 9 functional data patients who are all the patients that we had available 4 and above. 5 of those 8 are from the Phase I/II data that we've shared previously. Basically, the patients -- and this is all prospectively defined in our Phase I/II/III protocol, patients who were in the Phase I/II who meet the pivotal enrollment criteria are then carried over into the pivotal data set. So we were really excited to be able to add to that 5 an additional 4 subjects.

And you can see that with those 4 additional patients, we have high magnitude of effect and significant difference from external control by all the different ways that we look at that. So we're very encouraged. We'll continue to accrue additional data, which with more we anticipate, as raised earlier, this 9 patients demographically is very similar to all the other patients. So we're excited to keep going.

Operator: Our next question comes from Ellie Merle from Barclays.

Eliana Merle: So just to clarify on the FDA conversation. So when exactly did the FDA recommend a randomized controlled trial to you? I guess, was this in the recent meeting? Or I guess, is your press release referring to just general guidance from the FDA? If you could just clarify, I guess, when that was said, if it was said, and kind of the context around that? And then just a follow-up question. I know this was touched on a bit earlier. But I guess if the FDA recommends running a randomized controlled trial before filing when you do meet with them, what would your strategy then be with respect to filing in that scenario? Do you go ahead and file?

Or do you work on the design for the randomized control trial?

Curran Simpson: Thanks, Ellie. Yes, I think we have a pretty advanced design for an RCT-based study, which is intended for ex U.S., and we're planning to put that trial in action over the course of this year as we take a global approach to the program. So I think on a design standpoint, it's pretty straightforward. We have a great data set to pull from in terms of how we would design the study. I think the trigger to do so will be dependent on the conversations we have with FDA.

But I do want to caution again that completing an RCT study as a precursor to filing or a precursor to approval means that it's very unlikely that any new gene therapy would be approved until 2030. And I think that scenario is really untenable for the community and for -- it's the opposite of regulatory flexibility. So I think what we're saying is that our data using this external control strategy, which has been reviewed by FDA as well is going to meet the requirements associated with accelerated approval. And yes, if an RCT study is a requirement for a confirmatory study associated with that, we could always pivot our confirmatory study to meet that need.

That's not something that we would shy away from. So I think it's just a matter of going through the data with FDA. And then I believe that there will be sufficient opportunity for us to collaboratively solve that with FDA based on the conversations we've had recently with them.

Steve Pakola: And Steve here, I want to circle back as well to Sean, your other question of our IS regimen that is very targeted and which we believe our results are validating what we chose to do from the beginning. And fortunately, we haven't had to change this throughout the entire program. But since we have a panel with a couple of investigators who've used this immune regimen within the trial. So I can ask Dr. Panda and also Carolina to comment on your experience using this regimen. So let's start with you, Panda.

Aravindhan Veerapandiyan: Sure. Thanks, Steve. I think from a -- like I answered before from an immunosuppressive regimen standpoint, especially, I think eculizumab, we haven't seen any clinically complemented -- complement-mediated things like TMA or other issues related to complement. I think that speaks to probably due to eculizumab, immunosuppression or prophylaxis. Now from a comfort level standpoint, initially, when I first started, I had some reservations, but I think mainly because of -- can they have additional side effects because of all these agents that we are using. But we have dosed several patients who have used these eculizumab as well as sirolimus now, and this has been generally well tolerated by these patients.

So again, this experience gives us confidence to use this immunosuppressive regimen to prevent some of the side effects.

Steve Pakola: Carolina, anything to add?

Carolina Tesi Rocha: Yes. I fully agree with Panda. I initially felt the same concerns that the experience has been positive, both from me and my team handling this strong immunosuppressive regimen, but also from the families being able to cope with all the extra visits that they have for particularly the eculizumab infusions. So overall, quite positive and seeing the safety profile that is also encouraging to keep going.

Operator: Our next question comes from Daniil Gataulin of Chardan.

Daniil Gataulin: Congrats on the progress on the data. Just a quick one for me for microdystrophin expression. Maybe I missed it, but what are the age of participants who did not achieve the 10% microdystrophin expression? And were there any underlying characteristics that you believe prevented them from achieving that?

Curran Simpson: Thanks, Daniil. Steve, I'll send that one your way.

Steve Pakola: Sure. So this patient was in the 4 to 7 age range. There really wasn't anything demographically unique about this patient. I think it's just the reality that occasionally, unfortunately, it's rare that a patient and a family will choose not to get the biopsy based on their experience, for example, with the baseline one. So we, of course, get a baseline biopsy and measure. So again, all in all, missing one, we still have really impressive results in the 30 patients, about as good as we could hope for.

Operator: Our next question is from Paul Choi, Goldman Sachs.

Kyuwon Choi: Can you hear me now?

Steve Pakola: Yes.

Kyuwon Choi: My first question is for the panelists. With regard to the correlation that has been presented so far on the patients who are through 1 year and the relationship between microdystrophin and the functional results, the data are largely clustered in the middle here. And do you feel like 40% is sort of the minimum threshold you would need to see in terms of microdystrophin likely to result in a functional improvement? That's my first question. And my second question is just with regard to the FDA and just sort of any updated interim data that you might present. Can you clarify if you'll present any additional 1-year data cuts over the course of 2026?

Curran Simpson: Thanks, Paul. I'll take the second one, and then I'll ask Steve to work with the panel on your first question. Yes, I would expect that as the data set matures on function and patients cross the 12-month time point that we'll have updates on function. We don't have a specific time frame identified for that yet, but it will likely be sometime this fall. I'll move that over to Steve for the discussion on microdystrophin.

Steve Pakola: Sure. So the question of correlation and the particular clustering. One way to look at this is that the clustering is actually a good sign. It shows that the vast proportion of patients are having very good expression levels, which perhaps is really what's translating to the functional benefit. So I'll turn this to Dr. Panda since a lot of these patients were yours in the overall trial. How do you think of the correlation data and what this means for you when you think of what's the percent of microdystrophin that could lead to benefit?

Aravindhan Veerapandiyan: Thanks, Steve. I think I was quite impressed and surprised to see this direct correlation because I wasn't, to be honest, expecting this from our experience in general with gene therapy or other, even other dystrophin restoration therapies. I think this is quite impressive to show the function correlating with the dystrophin expression, though the n is small. I think from a cutoff standpoint, it's really hard to kind of say, I mean you have to have 40% because we have had -- we came up with, I think, the -- from an endpoint standpoint, 10% because we have seen that functional improvement with that 10% of microdystrophin expression.

So I wouldn't conclude from this analysis that you have to have 40% or 50% of microdystrophin expression to have function.

Operator: And our final question will come from Yi Chen, H.C. Wainwright.

Yi Chen: 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? And particularly, is there such a requirement for patients less than 4 years old?

Curran Simpson: Good to hear from you. In terms of the protocol, the pivotal protocol prespecified 30 patients for the pivotal program, and that was reviewed by FDA without comment. So we feel like from a safety standpoint, we have what we need to enact a filing. Having said that, we'll have more than that. We'll have closer to 50 by the time of filing based on immediately beginning to enroll and now rapidly enrolling the confirmatory study. So we feel and all of the benchmarks that we've been able to access support that, that should be a very adequate safety sample size, particularly given the low frequency of SAEs that we're seeing.

So I think that potential risk is very low in terms of submission strategy.

Operator: 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.