REGENXBIO Inc. (RGNX)

Item 2. Management’s Discussion and Analysis of Financial Condition and Results of Operations.

You should read the following discussion and analysis of our financial condition and results of operations in conjunction with the financial statements and the notes thereto included elsewhere in this Quarterly Report on Form 10-Q and with our audited financial statements and the notes thereto included in our Annual Report on Form 10-K for the year ended December 31, 2025, which we filed with the SEC on March 5, 2026. In addition, you should read the “Risk Factors” and “Information Regarding Forward-Looking Statements” sections of this Quarterly Report on Form 10-Q and our Annual Report on Form 10-K for the year ended December 31, 2025 for a discussion of important factors that could cause actual results to differ materially from the results described in or implied by the forward-looking statements contained in the following discussion and analysis.

Overview

We are a leading clinical-stage biotechnology company seeking to improve lives through the curative potential of gene therapy. Our investigational gene therapies are designed to deliver functional genes to address genetic defects in cells, enabling the production of therapeutic proteins or antibodies that are intended to impact disease. Through a single administration, gene therapy could potentially alter the course of disease significantly and deliver improved patient outcomes with long-lasting effects.

Overview of Product Candidates

We have developed a broad pipeline of gene therapy programs using our proprietary adeno-associated virus (AAV) gene therapy delivery platform (NAV Technology Platform) as a one-time treatment to address an array of diseases. Our lead programs and product candidates are described below.

Sura-vec (ABBV-RGX-314)

We are developing ABBV-RGX-314 (surabgene lomparvovec, sura-vec) in collaboration with AbbVie as a potential one-time treatment for chronic retinal conditions that cause total or partial vision loss, including wet age-related macular degeneration (wet AMD) and diabetic retinopathy (DR). In wet AMD, sura-vec is currently being evaluated in multiple clinical trials utilizing subretinal delivery, including two pivotal trials (ATMOSPHERE and ASCENT) where enrollment has been completed, one long-term follow-up study and a fellow eye sub-study. In DR, we are actively enrolling a pivotal, two-part Phase IIb/III study (NAAVIGATE) using suprachoroidal delivery. In addition to these late-stage pivotal programs, sura-vec is being evaluated in two Phase II clinical trials in patients with wet AMD (AAVIATE) and DR (ALTITUDE), which are ongoing along with two corresponding long-term follow-up studies, all utilizing in-office suprachoroidal delivery. Within the Phase II study in DR, we are also evaluating sura-vec in diabetic macular edema (DME). Sura-vec uses the NAV® AAV8 vector to deliver a gene encoding a therapeutic antibody fragment to inhibit vascular endothelial growth factor (VEGF). We have licensed certain exclusive rights to the SCS Microinjector® from Clearside Biomedical, Inc. (Clearside) to deliver gene therapy treatments to the suprachoroidal space of the eye.

Sura-vec for Treatment of Wet AMD

Subretinal Delivery

ATMOSPHERE® and ASCENT® are multi-center, randomized, active-controlled trials evaluating sura-vec versus ranibizumab and aflibercept, respectively. The primary endpoint is non-inferiority based on change from baseline in best-corrected visual acuity (BCVA) at 54 weeks and one year, respectively. Secondary endpoints include safety and tolerability, change in central retinal thickness (CRT) and need for supplemental anti-VEGF injections in the treatment arms.

Enrollment in the ATMOSPHERE and ASCENT pivotal trials for the treatment of patients with wet AMD using subretinal delivery was completed in October 2025. These trials, which together enrolled over 1,200 participants across more than 200 sites, are expected to support global regulatory submissions including with the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA). Topline data from these trials are expected to be announced in the fourth quarter of 2026 in partnership with AbbVie, with global regulatory submissions expected in 2027.

In July 2026, we presented long-term follow-up data from the Phase I/IIa trial that demonstrated a durable safety and efficacy profile through five years, with participants in Cohorts 3 and 4, who received subretinal sura-vec at doses similar to those being studied in the ATMOSPHERE and ASCENT pivotal trials, demonstrating stable to improved visual acuity and meaningful reductions in anti-VEGF treatment burden, with the exception of one participant in Cohort 4 with polypoidal choroidal vasculopathy refractory to anti-VEGF therapy.

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Suprachoroidal Delivery

The AAVIATE® trial is a multi-center, open label, randomized, controlled, dose-escalation Phase II trial to evaluate the efficacy, safety and tolerability of suprachoroidal delivery of sura-vec for the treatment of wet AMD. Based on the favorable safety profile observed as of July 29, 2024, the Phase II AAVIATE trial enrolled a cohort to evaluate sura-vec at dose level 4 (1.5x10e12 GC/eye). Patients in this cohort received short course prophylactic steroid eye drops. Enrollment of the AAVIATE trial has been completed.

Sura-vec for Treatment of DR and DME

In August 2025, we and AbbVie announced an amendment to our collaboration agreement and plans to initiate a pivotal program consisting of a Phase IIb/III trial (NAAVIGATE) as well as a second Phase III trial. NAAVIGATE is a two-part, multicenter, randomized, masked, sham-controlled Phase IIb/III study to evaluate the safety and efficacy of a one-time, in-office administration of sura-vec in subjects with non-proliferative diabetic retinopathy (NPDR) without center-involved diabetic macular edema (CI-DME). The primary endpoint is 2-step improvement on the Diabetic Retinopathy Severity Scale (DRSS) at one year. We are actively enrolling the Phase IIb/III NAAVIGATE trial and, in June 2026, dosed the first patient in the Phase IIb portion of the trial, upon which we earned a $100.0 million milestone payment that was received from AbbVie in July 2026. Following an interim analysis of part one (Phase IIb) of the NAAVIGATE trial, we and AbbVie expect to initiate a Phase III expansion, including part two (Phase III) of the U.S. NAAVIGATE trial and a parallel global trial led by AbbVie.

Concurrent with the August 2025 announcement, we announced positive two-year data from the Phase II ALTITUDE® trial. The ALTITUDE trial is a multi-center, open label, randomized, controlled, dose-escalation Phase II trial to evaluate the efficacy, safety and tolerability of sura-vec using suprachoroidal delivery for the treatment of DR. The positive two-year data showed sura-vec was well tolerated in subjects with NPDR at dose levels 1, 2, and 3. There were no drug-related serious adverse events and no intraocular inflammation was observed through two years at dose level 3 (1.0x1012 GC/eye) (n = 15) with short-course topical prophylactic steroids. Additionally, 50% of dose level 3 patients achieved at least a two-step improvement without need for any supplemental treatment.

In July 2026, we presented long-term follow-up data from the Phase II ALTITUDE trial that showed, among other findings, that participants at dose level 3 (1.0×10¹² GC/eye) with short-course prophylactic topical steroids, the same dose being evaluated in the Phase IIb/III NAAVIGATE trial, maintained a durable safety and efficacy profile through 2.5 years. 55% of participants achieved 2-step improvement on the DRSS without additional treatment, and 70% of participants experienced no vision-threatening events. These data are consistent with previously presented two-year dose level 3 NPDR data from the ALTITUDE trial and support the potential of one-time in-office sura-vec to modify the underlying disease and decrease risk of vision-threatening events.

RGX-202 for Treatment of Duchenne

We are developing RGX-202 as an investigational AAV therapeutic for the treatment of Duchenne muscular dystrophy (Duchenne), using the NAV AAV8 vector to deliver a transgene for a novel microdystrophin that includes the functional elements of the C-Terminal domain as well as a muscle-specific promoter to support a targeted therapy for improved resistance to muscle damage associated with Duchenne. Other differentiating elements of RGX-202 include the proactive immune suppression regimen and in-house, state-of-the-art manufacturing that has demonstrated leading purity levels in Duchenne (80% full capsids).

AFFINITY DUCHENNE® is an ongoing multicenter, open-label Phase I/II/III trial to evaluate the safety, tolerability and clinical efficacy of a one-time intravenous dose of RGX-202 in ambulatory patients with Duchenne aged 1 to 11 years old. Phase I/II results, reported between November 2024 and March 2026, demonstrated RGX-202 to be well tolerated with no serious adverse events or adverse events of special interest among all patients (n=13). Additionally, we reported positive biomarker data showing consistent, high expression and transduction of RGX-202 microdystrophin, with all patients exceeding 10%. Pivotal dose (2x1014 GC/kg) participants in the Phase I/II exceeded expected disease trajectory on the North Star Ambulatory Assessment (NSAA) and other timed function tests at one year using multiple validated methods to estimate expected disease progression without treatment (n=7). Notably, five participants for whom functional data has been reported were aged eight or older at dosing, when functional decline is expected.

In October 2025, we announced that enrollment had completed in the pivotal portion of AFFINITY DUCHENNE (n=approximately 30).

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In May 2026, we announced positive topline results from the pivotal Phase III AFFINITY DUCHENNE trial of RGX-202, including primary endpoint (n=30 at Week 12), interim safety (n=31) and interim functional data (n=9 at 12 months):

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The primary endpoint was achieved with high statistical significance; 93% of patients achieved RGX-202 microdystrophin expression above 10% (p0.0001).

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RGX-202 was well-tolerated and continued to demonstrate a favorable interim safety profile.

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RGX-202 demonstrated functional improvement and evidence of positively impacting disease trajectory at one year post-treatment, as measured by NSAA and timed function tests (Time to Stand, 10 Meter Walk-run, Time to Climb).

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Statistically significant correlation between RGX-202 microdystrophin expression level and functional improvement, supporting validity of surrogate endpoint.

As of May 2026, in recent discussions, the FDA shared that the use of RGX-202 microdystrophin expression as a surrogate endpoint will be based on the correlation analysis with clinical outcomes, which has been clearly demonstrated in our interim data. While the FDA has recommended a randomized controlled trial, it has guided that externally controlled trials may be adequate for demonstrating substantial evidence of effectiveness, especially when the treatment effect is sufficiently large enough to overcome limitations of externally controlled trials.

Given the positive topline pivotal data, continued favorable safety profile, and statistically significant correlation between microdystrophin and functional improvement, we plan to initiate a Biologics License Application (BLA) submission in the third quarter of 2026 under the accelerated approval pathway to support potential FDA approval in the second half of 2027.

In June 2026, we announced we had completed dosing in the confirmatory study of RGX-202 and our plan to include in our planned BLA a safety dataset from the AFFINITY DUCHENNE pivotal and confirmatory studies (n=63) as well as efficacy data from the pivotal portion (n=30), inc

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ITEM 7. MANAGEMENT’S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS

You should read the following discussion and analysis of our financial condition and results of operations in conjunction with the audited financial statements and the notes thereto included elsewhere in this Annual Report on Form 10-K. In addition, you should read the “Risk Factors” and “Information Regarding Forward-Looking Statements” sections of this Annual Report on Form 10-K for a discussion of important factors that could cause actual results to differ materially from the results described in or implied by the forward-looking statements contained in the following discussion and analysis.

For a full discussion and analysis of financial condition and results of operations for the year ended December 31, 2024, including a year-over-year comparison to the year ended December 31, 2023, please read the “Management's Discussion and Analysis of Financial Condition and Results of Operations” section of our Annual Report on Form 10-K for the year ended December 31, 2024, which we filed with the SEC on March 13, 2025.

Overview

We are a leading clinical-stage biotechnology company seeking to improve lives through the curative potential of gene therapy. Our investigational gene therapies are designed to deliver functional genes to address genetic defects in cells, enabling the production of therapeutic proteins or antibodies that are intended to impact disease. Through a single administration, gene therapy could potentially alter the course of disease significantly and deliver improved patient outcomes with long-lasting effects.

Overview of Product Candidates

We have developed a broad pipeline of gene therapy programs using our proprietary adeno-associated virus (AAV) gene therapy delivery platform (NAV Technology Platform) as a one-time treatment to address an array of diseases. Our lead programs and product candidates are described below:

•
ABBV-RGX-314: We are developing ABBV-RGX-314 (surabgene lomparvovec, sura-vec) in collaboration with AbbVie as a potential one-time treatment for chronic retinal conditions that cause total or partial vision loss, including wet age-related macular degeneration (wet AMD) and diabetic retinopathy (DR). ABBV-RGX-314 is currently being evaluated in multiple clinical trials, including two pivotal trials (ATMOSPHERE and ASCENT), one Phase II bridging study, one long-term follow-up study and a fellow eye sub-study in patients with wet AMD, all utilizing subretinal delivery. Additionally, two Phase II clinical trials in patients with wet AMD (AAVIATE) and DR (ALTITUDE) are ongoing along with two corresponding long-term follow-up studies, all utilizing in-office suprachoroidal delivery. Within the Phase II study in DR, we are also evaluating ABBV-RGX-314 in diabetic macular edema (DME). Additionally, we are planning a Phase IIb/III program in DR and expect to dose the first patient in a two-part Phase IIb/III study (NAAVIGATE) in the second quarter of 2026. ABBV-RGX-314 uses the NAV® AAV8 vector to deliver a gene encoding a therapeutic antibody fragment to inhibit vascular endothelial growth factor (VEGF). We have licensed certain exclusive rights to the SCS Microinjector® from Clearside Biomedical, Inc. (Clearside) to deliver gene therapy treatments to the suprachoroidal space of the eye.

Wet AMD

Subretinal Delivery

Enrollment in the ATMOSPHERE® and ASCENT® pivotal trials for the treatment of patients with wet AMD using subretinal delivery was completed in October 2025. These trials are expected to support global regulatory submissions with the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA). Topline data from these trials are expected to be shared in the fourth quarter of 2026 in partnership with AbbVie.

Suprachoroidal Delivery

The AAVIATE® trial is a multi-center, open label, randomized, controlled, dose-escalation Phase II trial to evaluate the efficacy, safety and tolerability of suprachoroidal delivery of ABBV-RGX-314 for the treatment of wet AMD.

Based on the favorable safety profile observed as of July 29, 2024, the Phase II AAVIATE trial enrolled a cohort to evaluate ABBV-RGX-314 at dose level 4 (1.5x10e12 GC/eye). Patients in this cohort received short course prophylactic steroid eye drops.

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DR and DME

The ALTITUDE® trial is a multi-center, open label, randomized, controlled, dose-escalation Phase II trial to evaluate the efficacy, safety and tolerability of ABBV-RGX-314 using suprachoroidal delivery for the treatment of DR. In November 2023, we announced data showing ABBV-RGX-314 was well tolerated at dose levels 1 and 2 and positive signals of efficacy, including 20.8% of patients exhibiting 2-step Diabetic Retinopathy Severity Scale (DRSS) improvement without additional DR treatment at one year.

In August 2025, we and AbbVie executed an amendment to our collaboration agreement and announced plans to initiate a pivotal program consisting of a Phase IIb/III trial (NAAVIGATE) as well as a second Phase III trial. NAAVIGATE is a Phase IIb/III multicenter, randomized, masked, sham-controlled study to evaluate the safety and efficacy of sura-vec in subjects with non-proliferative DR (NPDR) without center-involved diabetic macular edema (CI-DME). The primary endpoint is 2-step improvement on the diabetic retinopathy severity scale (DRSS) at one year. Following an interim analysis, REGENXBIO and AbbVie will initiate a Phase III expansion, which will include two Phase III trials, including a U.S. trial and a parallel global trial, led by AbbVie. We expect to dose the first patient in NAAVIGATE in the second quarter of 2026.

The ALTITUDE trial includes a new cohort of patients with center-involved DME evaluating ABBV-RGX-314 at dose level 4. Enrollment completed in this cohort in June 2025. DME is a vision-threatening complication of DR; an estimated 34 million people globally have DME. Patients received a one-time, in-office injection of ABBV-RGX-314 at dose level 4 (1.5x10e12 GC/eye) with short course prophylactic steroid eye drops.

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RGX-202: We are developing RGX-202 as an investigational AAV therapeutic for the treatment of Duchenne muscular dystrophy (Duchenne), using the NAV AAV8 vector to deliver a transgene for a novel microdystrophin that includes the functional elements of the C-Terminal domain as well as a muscle-specific promoter to support a targeted therapy for improved resistance to muscle damage associated with Duchenne. Other differentiating elements of RGX-202 include the proactive immune suppression regimen and in-house, state-of-the-art manufacturing that has demonstrated leading purity levels in Duchenne (80% full capsids).

AFFINITY DUCHENNE® is a multicenter, open-label Phase I/II/III trial to evaluate the safety, tolerability and clinical efficacy of a one-time intravenous dose of RGX-202 in patients with Duchenne aged one and older. The initiation of the pivotal study was designed to enroll approximately 30 patients in the U.S. and Canada.

In October 2025, we announced that enrollment in the AFFINITY DUCHENNE pivotal trial had completed and that we continue to enroll participants in the planned confirmatory trial. We expect to share topline data in the early second quarter of 2026 and request a pre-Biologics License Application (BLA) meeting with the FDA in mid-2026.

We began manufacturing the first batches of RGX-202 intended for commercial supply at our Manufacturing Innovation Center and completed the Process Performance Qualification (PPQ) campaign in the fourth quarter of 2025. Additional regulatory interactions with the FDA and the EMA are planned for 1H 2026.

We are also recruiting patients in the AFFINITY BEYOND® trial, an observational screening study. The primary objective is to evaluate the prevalence of AAV8 antibodies in patients with Duchenne up to 12 years of age. Information collected in this study may be used to identify potential participants for the AFFINITY DUCHENNE trial and potential future trials of RGX-202.

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RGX-121: We are developing RGX-121 (clemidsogene lanparvovec) in collaboration with Nippon Shinyaku in the United States and certain countries in Asia as an investigational one-time AAV therapeutic for the treatment of Mucopolysaccharidosis Type II (MPS II), also known as Hunter syndrome, using the NAV AAV9 vector to deliver the gene that encodes the iduronate-2-sulfatase enzyme.

A BLA for RGX-121 seeking accelerated approval was submitted to the FDA in March 2025. The FDA subsequently granted priority review of the BLA and successfully completed mid-cycle meeting, Pre-license inspection (PLI) and Bioresearch monitoring information (BIMO) inspections. The PLI and BIMO inspections were completed with no observations. In August 2025, we announced that the FDA review timeline had been extended following submission of 12-month clinical data for all patients in the pivotal study of RGX-121 (n=13) in response to an FDA information request. The Prescription Drug User Fee Act (PDUFA) goal date was extended from November 9, 2025 to February 8, 2026.

The longer-term data submitted to the FDA were presented at the International Congress of Inborn Errors of Metabolism (ICIEM) in September 2025. These results showed that in the pivotal phase of the CAMPSIITE trial (n=13), participants through one year sustained an 82% median reduction of cerebrospinal fluid (CSF) levels of HS D2S6. These longer-term data were consistent with previously reported topline pivotal results from the CAMPSIITE trial.

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In January 2026, we announced that the FDA placed the RGX-121 program on clinical hold in relation to a serious adverse event in a patient treated in the Phase I/II trial of RGX-111. The FDA cited the similarities in products, study populations, and shared risk between the clinical studies.

In February 2026, we announced that the FDA issued a Complete Response Letter (CRL) for the RGX-121 BLA. The FDA stated in the CRL that it had agreed to the study protocol in principle and outlined several reasons for not approving the gene therapy, including uncertainty regarding the study eligibility criteria to adequately define a population with neuronopathic disease (vs. attenuated disease), the comparability of the natural history external control to the study population, and the appropriateness of CSF HS D2S6 as a surrogate endpoint reasonably likely to predict clinical benefit. The CRL lists several potential paths forward, including a new study, treating additional patients and conducting longer-term follow up, and using an untreated control arm. Throughout active discussions during the BLA process, we believed we had addressed the points raised in the CRL through the submission of additional data and responses to numerous information requests. The FDA did not agree the data set provided substantial evidence of effectiveness to support approval of RGX-121 for the treatment of MPS II. We plan to request a Type A meeting with the FDA.

As of March 2026, we plan to work with the FDA to address the clinical hold and CRL, and discuss potential paths forward for the program, Potential approval of the BLA for RGX-121 could result in receipt of a Rare Pediatric Disease Priority Review Voucher (PRV), assuming the statutory criteria are met. If approved, RGX-121 would be the first approved gene therapy and one-time treatment for MPS II.

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RGX-111: We are developing RGX-111 in collaboration with Nippon Shinyaku in the United States and certain countries in Asia as an investigational one-time AAV therapeutic for the treatment of Mucopolysaccharidosis Type I (MPS I), also known as Hurler syndrome, using the NAV AAV9 vector to deliver the IDUA gene.

In November 2023, future development of RGX-111 was halted as a result of a strategic pipeline prioritization and corporate restructuring. Prior to that announcement, RGX-111 demonstrated to

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