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Aligned with FDA on content of BLA and plans for submission: Submission of a rolling BLA using the accelerated approval pathway expected to start in Q3 2024 Confirmatory trial expected to begin in H2 2025 FDA confirmed RGX-121 commercial bulk drug is comparable to clinical material Positive biomarker, neurocognitive and systemic data will be part of BLA submission ROCKVILLE, Md., June 18, 2024 /PRNewswire/ -- REGENXBIO Inc. (Nasdaq: RGNX) today announced it completed a successful Pre-Biologics License Application (BLA) meeting for RGX-121 for the treatment Mucopolysaccharidosis Type II (MPS II), where it finalized details of its BLA with the U.S. Food and Drug Administration (FDA). The FDA continues to be aligned with REGENXBIO's plan to use cerebrospinal fluid (CSF) levels of heparan sulfate (HS) D2S6, a key biomarker of brain disease activity, as a surrogate endpoint reasonably likely to predict clinical benefit to support accelerated approval of RGX-121. Additionally, REGENXBIO and the FDA discussed manufacturing, non-clinical, device delivery system and other critical elements of the BLA, including a confirmatory study designed to verify and describe the predicted clinical benefit. REGENXBIO completed its database lock for the pivotal program and expects to initiate submission of a rolling BLA in the third quarter of 2024. REGENXBIO expects an FDA inspection of its Manufacturing Innovation Center in the first half of 2025. Commercial bulk drug and clinical trial material, both manufactured using REGENXBIO's proprietary NAVXpress™ platform process, were confirmed to be comparable. A confirmatory study of RGX-121 is expected to initiate enrollment in the second half of 2025, prior to potential FDA approval. Based on an expected priority review, potential approval of the planned BLA could result in receipt of a Rare Pediatric Disease Priority Review Voucher in 2025. "This positive engagement with the FDA marks an important milestone for REGENXBIO and RGX-121 on the path towards potential approval of the first gene therapy for Hunter syndrome," said Curran Simpson, Chief Operating Officer of REGENXBIO and President and CEO-elect. "Alignment with the FDA on important elements of this BLA, like our proprietary NAVXpress™ platform process and inspection of our commercial-ready manufacturing facility, provide a solid foundation as we advance to pivotal stage for our other rare program, RGX-202, and work to diligently to expedite its development for the Duchenne community." "The MPS II community is in need of new treatment options that have the potential to address the neurocognitive impacts of this devastating disease," said Dr. Matthew Ellinwood, Chief Scientific Officer of the National MPS Society. "We are pleased with REGENXBIO's continued positive discussions with and are encouraged by the totality of the biomarker, neurocognitive and systemic data for RGX-121 and the impact its potential approval may have for the families we serve." Topline results from the Phase I/II/III CAMPSIITE® trial of RGX-121 presented earlier this year demonstrated that the pivotal phase of the trial met its primary endpoint with statistical significance. Pivotal results were consistent with data from the dose-finding phase of CAMPSIITE, in which the majority of patients were shown to be exceeding expectations in neurodevelopmental function compared to natural history data up to four years. Long-term follow-up of patients treated with RGX-121 also showed there was a high rate of patients for whom trial investigators chose to discontinue standard-of-care intravenous enzyme replacement therapy (ERT) or were allowed to remain ERT-naïve. As of January 3, 2024, RGX-121 continues to be well tolerated in 25 patients dosed across all phases of the CAMPSIITE trial. REGENXBIO expects to share additional safety and efficacy data from the CAMPSIITE trial in the second half of 2024. About the CAMPSIITE® Trial CAMPSIITE is a Phase I/II/III multicenter, open-label trial for boys aged four months up to five years with neuronopathic MPS II. The primary endpoint of the trial is measurement of CSF GAGs. Accurate and sensitive measurements of CSF GAGs, such as HS D2S6, have the potential to be considered a surrogate endpoint that is reasonably likely to predict clinical benefit in MPS II disease under the accelerated approval pathway, as buildup of GAGs in the CSF of MPS II patients correlates with clinical manifestations including neurodevelopmental deficits. The pivotal program is using commercial-scale cGMP material from REGENXBIO's proprietary, high-yielding suspension-based manufacturing process, named NAVXpress™. In addition to measuring GAGs in the CSF, the trial will continue to collect neurodevelopmental data and caregiver-reported outcomes. About RGX-121 RGX-121 is a potential one-time AAV therapeutic for the treatment of boys with MPS II. RGX-121 expressed protein is structurally identical to normal I2S. RGX-21 Delivery of the IDS gene within cells in the CNS could provide a permanent source of secreted I2S beyond the blood-brain barrier, allowing for long-term cross correction of cells throughout the CNS. RGX-121 has received Orphan Drug Product, Rare Pediatric Disease, Fast Track and Regenerative Medicine Advanced Therapy designations from the U.S. Food and Drug Administration and advanced therapy medicinal products (ATMP) classification from the European Medicines Agency. About Mucopolysaccharidosis Type II (MPS II) MPS II, or Hunter Syndrome, is a rare, X-linked recessive disease caused by a deficiency in the lysosomal enzyme iduronate-2-sulfatase (I2S) leading to an accumulation of glycosaminoglycans (GAGs), including heparan sulfate (HS) in tissues which ultimately results in cell, tissue, and organ dysfunction, including in the central nervous system (CNS). MPS II is estimated to occur in 1 in 100,000 to 170,000 births. In severe forms of the disease, early developmental milestones may be met, but developmental delay is readily apparent by 18 to 24 months. Specific treatment to address the neurological manifestations of MPS II remains a significant unmet medical need. Key biomarkers of I2S enzymatic activity in MPS II patients include its substrate HS D2S6, which has been shown to correlate with neurocognitive manifestations of the disorder. ABOUT REGENXBIO Inc. REGENXBIO is a leading clinical-stage biotechnology company seeking to improve lives through the curative potential of gene therapy. Since its founding in 2009, REGENXBIO has pioneered the development of AAV Therapeutics, an innovative class of gene therapy medicines. REGENXBIO is advancing a pipeline of AAV Therapeutics for retinal and rare diseases, including ABBV-RGX-314 for the treatment of wet AMD and diabetic retinopathy, being developed in collaboration with AbbVie, RGX-202 for the treatment of Duchenne and RGX-121 for the treatment of MPS II. Thousands of patients have been treated with REGENXBIO's AAV Therapeutic platform, including Novartis' ZOLGENSMA for children with spinal muscular atrophy. Designed to be one-time treatments, AAV Therapeutics have the potential to change the way healthcare is delivered for millions of people. For more information, please visit . FORWARD-LOOKING STATEMENTS This press release includes "forward-looking statements," within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. These statements express a belief, expectation or intention and are generally accompanied by words that convey projected future events or outcomes such as "believe," "may," "will," "estimate," "continue," "anticipate," "assume," "design," "intend," "expect," "could," "plan," "potential," "predict," "seek," "should," "would" or by variations of such words or by similar expressions. The forward-looking statements include statements relating to, among other things, REGENXBIO's future operations and clinical trials. 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Refer to the "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations" sections of REGENXBIO's Annual Report on Form 10-K for the year ended December 31, 2023, and comparable "risk factors" sections of REGENXBIO's Quarterly Reports on Form 10-Q and other filings, which have been filed with the U.S. Securities and Exchange Commission (SEC) and are available on the SEC's website at WWW.SEC.GOV. All of the forward-looking statements made in this press release are expressly qualified by the cautionary statements contained or referred to herein. The actual results or developments anticipated may not be realized or, even if substantially realized, they may not have the expected consequences to or effects on REGENXBIO or its businesses or operations. Such statements are not guarantees of future performance and actual results or developments may differ materially from those projected in the forward-looking statements. Readers are cautioned not to rely too heavily on the forward-looking statements contained in this press release. These forward-looking statements speak only as of the date of this press release. Except as required by law, REGENXBIO does not undertake any obligation, and specifically declines any obligation, to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise. Zolgensma® is a registered trademark of Novartis Gene Therapies. All other trademarks referenced herein are registered trademarks of REGENXBIO. Contacts: Dana Cormack Corporate Communications dcormack@regenxbio.com Investors: Chris Brinzey ICR Westwicke 339-970-2843 chris.brinzey@westwicke.com Company Codes: NASDAQ-NMS:RGNX

Sept. 14, 2022 11:28 UTC First in-human pediatric Phase 1/2 study to evaluate the safety and tolerability of first-in-class gene therapy targeting infants age ≥3 months and ≤12 months, diagnosed with nMPS-II University of Manchester (U.K.) expects to initiate clinical trial later this year U.S. Food and Drug Administration (FDA) previously granted rare pediatric disease and orphan drug designations for AVR-RD-05, AVROBIO’s investigational gene therapy for nMPS-II or Hunter syndrome CAMBRIDGE, Mass.--(BUSINESS WIRE)-- AVROBIO Inc. (Nasdaq: AVRO), a leading clinical-stage gene therapy company working to free people from a lifetime of genetic disease, today announced that the U.K. Medicines and Healthcare Products Regulatory Agency (MHRA), Research Ethics Committee (REC) and Health Research Authority (HRA) have approved the clinical trial application (CTA) submitted by AVROBIO’s collaborators at the University of Manchester, U.K. (UoM) for initiation of the Phase 1/2 clinical trial of investigational autologous hematopoietic stem cell (HSC) gene therapy in infants diagnosed with neuronopathic mucopolysaccharidosis type II (nMPS-II) or Hunter syndrome. This rare and seriously debilitating lysosomal disorder primarily affects young males. UoM’s 24-month, non-randomized, open label study will enroll up to five children aged ≥3 months and ≤12 months diagnosed with nMPS-II to evaluate the safety and tolerability, pharmacodynamic and clinical efficacy of HSC gene therapy. The gene therapy, which AVROBIO refers to as AVR-RD-05, is designed to transduce autologous (a patient’s own) HSCs ex vivo with a lentiviral vector encoding a brain-targeted iduronate-2-sulfatase (IDS) enzyme, which is deficient in these patients. “We are thrilled to collaborate with the team at UoM to bring to infants and families living with Hunter syndrome a potential one-time therapy for this devastating disease. Hunter syndrome causes complications throughout the body, including severe neurological, cardiac and respiratory dysfunction, skeletal malformations and hearing impairment," said Geoff MacKay, president and CEO of AVROBIO. “This investigational HSC gene therapy which includes CNS-targeted gene expression has been designed to express supra-physiological levels of the IDS enzyme in transduced HSCs, with the intent to correct both the systemic and neurological manifestations of this disease.” UoM expects to dose the first patient in the trial in 1H 2023. The study will be overseen by Robert Wynn, M.D., professor of Pediatric Hematology at Royal Manchester Children’s Hospital, part of Manchester University NHS Foundation Trust; Brian Bigger, Ph.D., professor of Cell and Gene Therapy at The University of Manchester; and Simon Jones, M.D., professor of Pediatric Inherited Metabolic Diseases at the Manchester Centre for Genomic Medicine at Saint Mary’s Hospital, part of Manchester University NHS Foundation Trust. “It’s incredibly exciting to have the opportunity to test our investigational brain-targeted HSC gene therapy in boys with Hunter disease,” said Professor Bigger. “There are currently no available treatments that target the brain in this devastating disorder, so the approach of tagging the IDS enzyme with a blood-brain-barrier crossing peptide will enable us to see if this approach can improve outcomes for patients.” Professor Bigger has previously published preclinical data demonstrating that HSC gene therapy deploying a proprietary blood-brain-barrier crossing ApoEII tag fused to the human IDS gene, drives expression of IDS-ApoEII in blood cells, enabling both blood cells that naturally traffic into the brain in traditional HSC gene therapy and peripheral brain targeted IDS-ApoEII enzyme to both cross the blood-brain barrier, thus potentially addressing peripheral disease and normalizing brain pathology. In these mouse models of Hunter syndrome, brain-targeted HSC gene therapy showed improvement across multiple metrics, including normalization of skeletal features such as the cheekbone dimensions, the width of the humerus and femur bones, correction of neurons in the brain and the preservation of higher brain functions including working memory. To find out more about the trial, contact mpsiitrial@manchester.ac.uk, Simon.Jones@mft.nhs.uk or Robert.wynn@mft.nhs.uk. Previously, the U.S. Food and Drug Administration (FDA) granted rare pediatric disease and orphan drug designations for AVR-RD-05. About Hunter syndrome Hunter syndrome is caused by a deficiency in the lysosomal enzyme iduronate-2-sulfatase (IDS), which is essential for breaking down large sugar molecules. It affects an estimated one in 100,000 to one in 170,000 males worldwide. Children with severe cases of Hunter syndrome typically show early symptoms of the disease in infancy and childhood and begin to regress developmentally, losing basic motor skills and cognitive function over a few years. The neuronopathic form of MPSII is characterized by cognitive, language and motor skills declining early in childhood. The current standard of care is weekly enzyme replacement therapy (ERT), which can delay some peripheral disease complications but does not halt overall progression of the disease and has not been demonstrated to address the central nervous system (CNS) issues. Even with ERT, people with Hunter syndrome face life-limiting symptoms and a significantly reduced lifespan. About AVROBIO Our vision is to bring personalized gene therapy to the world. We target the root cause of genetic disease by introducing a functional copy of the affected gene into patients’ own hematopoietic stem cells (HSCs), with the goal to durably express the therapeutic protein throughout the body, including the central nervous system. Our first-in-class pipeline includes clinical programs for cystinosis and Gaucher disease type 1, as well as preclinical programs for Gaucher disease type 3, Hunter syndrome and Pompe disease. Our proprietary plato® gene therapy platform is designed to be scaled to support late-stage clinical development and commercialization globally. We are headquartered in Cambridge, Mass. For additional information, visit avrobio.com, and follow us on Twitter and LinkedIn. Forward-Looking Statements This press release contains forward-looking statements, including statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements may be identified by words and phrases such as “aims,” “anticipates,” “believes,” “could,” “designed to,” “estimates,” “expects,” “forecasts,” “goal,” “intends,” “may,” “plans,” “possible,” “potential,” “seeks,” “will,” and variations of these words and phrases or similar expressions that are intended to identify forward-looking statements. These forward-looking statements include, without limitation, statements regarding our business strategy for and the potential therapeutic benefits of our preclinical and clinical product candidates, including AVR-RD-05 for the treatment of nMPSII or Hunter syndrome, the potential benefits and incentives provided by the FDA’s rare pediatric disease and orphan drug designations for AVR-RD-05, statements regarding the expectations or activities of our collaborators including timing of clinical trial initiation and dosing of patients, the design, commencement, enrollment and timing of planned clinical trials, preclinical or clinical trial results, product approvals and regulatory pathways, our plans and expectations with respect to interactions with regulatory agencies, anticipated benefits of our gene therapy platform including potential impact on our commercialization activities, timing and likelihood of success, the expected benefits and results of our implementation of the plato platform in our clinical trials and gene therapy programs, and the expected safety pro our preclinical and investigational gene therapies. Any such statements in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Results in preclinical or early-stage clinical trials may not be indicative of results from later stage or larger scale clinical trials and do not ensure regulatory approval. You should not place undue reliance on these statements, or the scientific data presented. Any forward-looking statements in this press release are based on AVROBIO’s current expectations, estimates and projections about our industry as well as management’s current beliefs and expectations of future events only as of today and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, the risk that any one or more of AVROBIO’s product candidates will not be successfully developed or commercialized, the risk of cessation or delay of any ongoing or planned clinical trials of AVROBIO or our collaborators, the risk that AVROBIO may not successfully recruit or enroll a sufficient number of patients for our clinical trials, the risk that AVROBIO may not realize the intended benefits of our gene therapy platform, including the features of our plato® platform, the risk that our product candidates or procedures in connection with the administration thereof will not have the safety or efficacy pro we anticipate, the risk that prior results, such as signals of safety, activity or durability of effect, observed from preclinical or clinical trials, will not be replicated or will not continue in ongoing or future studies or trials involving AVROBIO’s product candidates, the risk that we will be unable to obtain and maintain regulatory approval for our product candidates, the risk that the size and growth potential of the market for our product candidates will not materialize as expected, risks associated with our dependence on third-party suppliers and manufacturers, risks regarding the accuracy of our estimates of expenses and future revenue, risks relating to our capital requirements and needs for additional financing, risks relating to clinical trial and business interruptions resulting from the COVID-19 outbreak or similar public health crises, including that such interruptions may materially delay our enrollment and development timelines and/or increase our development costs or that data collection efforts may be impaired or otherwise impacted by such crises, and risks relating to our ability to obtain and maintain intellectual property protection for our product candidates. For a discussion of these and other risks and uncertainties, and other important factors, any of which could cause AVROBIO’s actual results to differ materially and adversely from those contained in the forward-looking statements, see the section entitled “Risk Factors” in AVROBIO’s most recent Annual or Quarterly Report, as well as discussions of potential risks, uncertainties and other important factors in AVROBIO’s subsequent filings with the Securities and Exchange Commission. AVROBIO explicitly disclaims any obligation to update any forward-looking statements except to the extent required by law.

July 13, 2022 11:00 UTC AVR-RD-05 is the fourth AVROBIO gene therapy to receive orphan drug designation FDA previously granted rare pediatric disease designation for AVR-RD-05 CAMBRIDGE, Mass.--(BUSINESS WIRE)-- AVROBIO, Inc. (Nasdaq: AVRO), a leading clinical-stage gene therapy company with a shared purpose to free people from a lifetime of genetic disease, today announced that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation for AVR-RD-05, its gene therapy for the treatment of mucopolysaccharidosis type II (MPSII), or Hunter syndrome, a rare and seriously debilitating lysosomal disorder that primarily affects young boys. Orphan drug designation is granted by FDA to drugs and biologics that are intended for the safe and effective treatment, diagnosis or prevention of rare diseases or conditions that affect fewer than 200,000 people in the U.S. Orphan drug designation provides certain incentives, which may include tax credits towards the cost of clinical trials and prescription drug user fee waivers. Hunter syndrome is caused by a deficiency in the lysosomal enzyme iduronate-2-sulfatase (IDS), which is essential for breaking down large sugar molecules. The gene therapy uses a patient’s own hematopoietic stem cells (HSCs) that are transduced ex vivo with a lentiviral vector encoding the human IDS enzyme. The company’s planned collaborator-sponsored Phase 1/2 clinical trial for Hunter syndrome is expected to commence in 2023 under the company’s collaboration with the University of Manchester, UK. The program was developed by Brian Bigger, Ph.D., professor of cell and gene therapy at the University of Manchester, who has previously published preclinical data demonstrating that HSC gene therapy deploying an optimized, proprietary tag has the potential to correct peripheral disease and normalize brain pathology. About Hunter syndrome Hunter syndrome, which affects an estimated one in 100,000 to one in 170,000 males worldwide, causes devastating complications throughout the body, including severe neurological, cardiac and respiratory dysfunction, skeletal malformations and hearing impairment. Children with severe cases of Hunter syndrome typically show early symptoms of the disease in infancy and childhood and begin to regress developmentally, losing basic motor skills and cognitive function over a few years. The current standard of care is weekly enzyme replacement therapy (ERT), which can delay some health complications but does not halt overall progression of the disease and has not been demonstrated to address the central nervous system (CNS) issues. Even with ERT, people with Hunter syndrome face life-limiting symptoms and a significantly reduced lifespan. About AVROBIO Our vision is to bring personalized gene therapy to the world. We aim to prevent, halt or reverse disease throughout the body with a single dose of gene therapy designed to drive durable expression of therapeutic protein, even in hard-to-reach tissues and organs including brain, muscle and bone. AVROBIO’s pipeline is powered by our industry-leading plato® gene therapy platform, our foundation designed to deliver gene therapy worldwide. It includes clinical programs in cystinosis and Gaucher disease type 1, as well as preclinical programs in Gaucher disease type 3, Hunter syndrome and Pompe disease. We are headquartered in Cambridge, Mass. For additional information, visit avrobio.com, and follow us on Twitter and LinkedIn. Forward-Looking Statements This press release contains forward-looking statements, including statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements may be identified by words and phrases such as “aims,” “anticipates,” “believes,” “could,” “designed to,” “estimates,” “expects,” “forecasts,” “goal,” “intends,” “may,” “plans,” “possible,” “potential,” “seeks,” “will,” and variations of these words and phrases or similar expressions that are intended to identify forward-looking statements. These forward-looking statements include, without limitation, statements regarding our business strategy for and the potential therapeutic benefits of our preclinical and clinical product candidates, including AVR-RD-05 for the treatment of Hunter syndrome, the potential benefits and incentives provided by the FDA’s orphan drug designation for AVR-RD-05, the design, commencement, enrollment and timing of planned clinical trials, preclinical or clinical trial results, product approvals and regulatory pathways, our plans and expectations with respect to interactions with regulatory agencies, anticipated benefits of our gene therapy platform including potential impact on our commercialization activities, timing and likelihood of success, the expected benefits and results of our implementation of the plato platform in our clinical trials and gene therapy programs, and the expected safety pro our preclinical and investigational gene therapies. Any such statements in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Results in preclinical or early-stage clinical trials may not be indicative of results from later stage or larger scale clinical trials and do not ensure regulatory approval. You should not place undue reliance on these statements, or the scientific data presented. Any forward-looking statements in this press release are based on AVROBIO’s current expectations, estimates and projections about our industry as well as management’s current beliefs and expectations of future events only as of today and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, the risk that any one or more of AVROBIO’s product candidates will not be successfully developed or commercialized, the risk of cessation or delay of any ongoing or planned clinical trials of AVROBIO or our collaborators, the risk that AVROBIO may not successfully recruit or enroll a sufficient number of patients for our clinical trials, the risk that AVROBIO may not realize the intended benefits of our gene therapy platform, including the features of our plato® platform, the risk that our product candidates or procedures in connection with the administration thereof will not have the safety or efficacy pro we anticipate, the risk that prior results, such as signals of safety, activity or durability of effect, observed from preclinical or clinical trials, will not be replicated or will not continue in ongoing or future studies or trials involving AVROBIO’s product candidates, the risk that we will be unable to obtain and maintain regulatory approval for our product candidates, the risk that the size and growth potential of the market for our product candidates will not materialize as expected, risks associated with our dependence on third-party suppliers and manufacturers, risks regarding the accuracy of our estimates of expenses and future revenue, risks relating to our capital requirements and needs for additional financing, risks relating to clinical trial and business interruptions resulting from the COVID-19 outbreak or similar public health crises, including that such interruptions may materially delay our enrollment and development timelines and/or increase our development costs or that data collection efforts may be impaired or otherwise impacted by such crises, and risks relating to our ability to obtain and maintain intellectual property protection for our product candidates. For a discussion of these and other risks and uncertainties, and other important factors, any of which could cause AVROBIO’s actual results to differ materially and adversely from those contained in the forward-looking statements, see the section entitled “Risk Factors” in AVROBIO’s most recent Quarterly Report, as well as discussions of potential risks, uncertainties and other important factors in AVROBIO’s subsequent filings with the Securities and Exchange Commission. AVROBIO explicitly disclaims any obligation to update any forward-looking statements except to the extent required by law.