A Randomized, Partially Masked, Controlled, Phase 3 Clinical Study to Evaluate the Efficacy and Safety of RGX-314 Gene Therapy in Participants With nAMD

RGX-314 is being developed as a novel one-time gene therapy for the treatment of neovascular (wet) age-related macular degeneration (wet AMD). Wet AMD is characterized by loss of vision due to new, leaky blood vessel formation in the retina. Wet AMD is a significant cause of vision loss in the United States, Europe and Japan, with up to 2 million people living with wet AMD in these geographies alone. Current anti-VEGF therapies have significantly changed the landscape for treatment of wet AMD, becoming the standard of care due to their ability to prevent progression of vision loss in the majority of patients. These therapies, however, require life-long intraocular injections, typically repeated every four to 12 weeks in frequency, to maintain efficacy. Due to the burden of treatment, patients often experience a decline in vision with reduced frequency of treatment over time. RGX-314 is being developed as a potential one-time treatment for wet AMD.

Start Date28 Dec 2021

Sponsor / Collaborator

AbbVie, Inc.

NCT04832724 / CompletedPhase 2

A Phase 2, Open-label Study to Explore the Pharmacodynamics of Two Doses in Two Formulations of RGX-314 Gene Therapy Administered Via Subretinal Delivery in Participants With Neovascular Age-related Macular Degeneration

RGX-314 is being developed as a novel one-time gene therapy for the treatment of neovascular (wet) age-related macular degeneration (nAMD) also referred to as Wet AMD. Wet AMD is characterized by loss of vision due to new, leaky blood vessel formation in the retina. The purpose of this phase 2, open label study is to evaluate whether different doses of RGX-314 from two different formulations (clinical versus eventual commercial formulation) perform the same in humans when delivered by subretinal administration

Start Date22 Feb 2021

Sponsor / Collaborator

AbbVie, Inc.

NCT04704921 / RecruitingPhase 2/3

A Randomized, Partially Masked, Controlled, Phase 2b/3 Clinical Study to Evaluate the Efficacy and Safety of RGX-314 Gene Therapy in Participants With nAMD (ATMOSPHERE)

Start Date29 Dec 2020

Sponsor / Collaborator

AbbVie, Inc.

100 Clinical Results associated with RGX-314

100 Translational Medicine associated with RGX-314

100 Patents (Medical) associated with RGX-314

Literatures (Medical) associated with RGX-314

03 Oct 2022·Expert opinion on investigational drugs

Investigational drugs in clinical trials for macular degeneration

Review

Author: Tolentino, Michael J ; Tolentino, Andrew J

INTRODUCTION:

Intravitreal anti-vascular endothelial growth factor (VEGF) injections for exudative age-related macular degeneration (eAMD) are effective and safe but require frequent injections and have nonresponding patients. Geographic atrophy/dry AMD (gaAMD) remains an unmet medical need. New therapies are needed to address this leading cause of blindness in the increasing aged population.

AREAS COVERED:

This paper reviews the pathogenesis of macular degeneration, current and failed therapeutics, therapies undergoing clinical trials and a rationale for why certain AMD therapies may succeed or fail.

EXPERT OPINION:

VEGF-inhibitors reduce both vascular leakage and neovascularization. Experimental therapies that only address neovascularization or leakage will unlikely supplant anti-VEGF therapies. The most promising future therapies for eAMD, are those that target, more potently inhibit and have a more sustained effect on the VEGF pathway such as KSI-301, RGX-314, CLS-AX, EYEP-1901, OTX-TKI. GaAMD is a phenotype of phagocytic retinal cell loss. Inhibiting phagocytic activity of retinal microglial/macrophages at the border of geographic atrophy and reducing complement derived activators of microglial/macrophage is the most promising strategy. Complement inhibitors (Pegcetacoplan and Avacincaptad pegol) will likely obtain FDA approval but will serve to pave the way for combined complement and direct phagocytic inhibitors such as AVD-104.

01 Feb 2022·Eye (London, England)Q3 · MEDICINE

Review of gene therapies for age-related macular degeneration

Q3 · MEDICINE

Review

Author: Danzig, Carl J ; Yiu, Glenn ; Kaiser, Peter K ; Waheed, Nadia K ; Aziz, Aamir A ; Weng, Christina Y ; Thomas, Mathew J ; Khanani, Arshad M ; Kiss, Szilárd

Gene therapies aim to deliver a therapeutic payload to specified tissues with underlying protein deficiency. Since the 1990s, gene therapies have been explored as potential treatments for chronic conditions requiring lifetime care and medical management. Ocular gene therapies target a range of ocular disorders, but retinal diseases are of particular importance due to the prevalence of retinal disease and the current treatment burden of such diseases on affected patients, as well as the challenge of properly delivering these therapies to the target tissue. The purpose of this review is to provide an update on the most current data available for five different retinal gene therapies currently undergoing clinical trials for use against age-related macular degeneration (AMD) and the development of novel delivery routes for the administration of such therapies. Research has been performed and compiled from PubMed and the select authors of this manuscript on the treatment and effectiveness of five current retinal gene therapies: Luxturna, ADVM-022, RGX-314, GT-005, and HMR59. We present the available data of current clinical trials for the treatment of neovascular and dry age-related macular degeneration with different AAV-based gene therapies. We also present current research on the progress of developing novel routes of administration for ocular gene therapies. Retinal gene therapies offer the potential for life-changing treatment for chronic conditions like age-related macular degeneration with a single administration. In doing so, gene therapies change the landscape of treatment options for these chronic conditions for both patient and provider.

13 Oct 2019·Expert opinion on pharmacotherapyQ3 · MEDICINE

Innovative therapies for neovascular age-related macular degeneration

Q3 · MEDICINE

Review

Author: Ciulla, Thomas A. ; Al-Khersan, Hasenin ; Dugel, Pravin U. ; Hussain, Rehan M.

Introduction: Investigational anti-VEGF treatments for neovascular age-related macular degeneration (nAMD) aim to improve visual outcomes and reduce treatment burden; these include long-acting agents, combination strategies, topical agents, sustained-release, and genetic therapies. Areas covered: The authors provide a comprehensive review of investigational therapies for nAMD, focusing on therapies currently in clinical trial. Expert opinion: Long-acting anti-VEGF agents have demonstrated promising results in phase 3 studies, and include Brolucizumab, a single-chain antibody fragment, and Abicipar, a designed ankyrin repeat protein (DARPin). Other unique anti-VEGF agents in current trials include Conbercept - a fusion protein of the VEGF receptor domains, KSI-301 - an anti-VEGF antibody biopolymer conjugate, and OPT-302 - an inhibitor of VEGF-C/D. Strategies to activate the Tie-2 receptor, some in combination with VEGF inhibition, are of interest, with recent trials of Faricimab, ARP-1536, and nesvacumab. Topical anti-VEGF ± anti-PDGF agents, such as pazopanib, squalamine lactate, regorafenib, and LHA510 have shown limited efficacy and/or have not been advanced, although PAN-90806 continues to advance with promising initial results. Sustained-release anti-VEGF treatments, to address treatment burden, include the ranibizumab Port Delivery System, GB-102, NT-503, hydrogel depot, Durasert, and ENV1305. Similarly, genetic therapies, including RGX-314 and ADVM-022, aim to provide sustained anti-VEGF expression from the retina.

News (Medical) associated with RGX-314

24 Jun 2024

·www.biospace.com

REGENXBIO Announces Expansion of AFFINITY DUCHENNE® Trial to Include a New Cohort of Younger Patients

Company to begin enrollment of patients aged 1-3 years Expects data from younger cohort to be part of pivotal plans and BLA filing for broad label End-of-Phase II meeting with FDA scheduled for late July to finalize pivotal program design Based on recent commercial landscape, confirmed accelerated approval pathway remains available given ongoing unmet need and RGX-202 differentiated design Remains on track to initiate pivotal trial in late Q3 to early Q4 2024 The next potential therapy to become available for Duchenne patients ROCKVILLE, Md., June 24, 2024 /PRNewswire/ -- REGENXBIO Inc. (Nasdaq: RGNX) today announced it initiated enrollment in a new cohort of patients ages 1-3 in its Phase I/II AFFINITY DUCHENNE® trial to evaluate the safety and efficacy of RGX-202 in boys with Duchenne muscular dystrophy (Duchenne). RGX-202 is an investigational one-time AAV Therapeutic targeted to deliver a novel microdystrophin, representing the next wave of innovative design in Duchenne gene therapy. RGX-202 is the only gene therapy approved or in development for Duchenne that incorporates the C-Terminal domain, making the RGX-202 transgene the closest to the naturally occurring dystrophin gene. With this announcement, REGENXBIO is enrolling ambulatory boys with Duchenne aged 1 to 11 in the AFFINITY DUCHENNE trial. The new cohort is expected to enroll up to five patients aged 1-3 to receive RGX-202 at the pivotal dose level (2x1014 genome copies (GC)/kg body weight). Additionally, REGENXBIO has confirmed an end-of-Phase II (EOP2) meeting is scheduled with the FDA at the end of July. This meeting is expected to finalize the AFFINITY DUCHENNE pivotal trial design, with the goal of continuing to expedite the development of RGX-202. The Company anticipates that all patients enrolled at dose level 2 (n=12) will be included in its pivotal trial data set. The Company plans to use RGX-202 microdystrophin expression as a surrogate endpoint to support a Biologics License Application (BLA) submission using the accelerated approval pathway with the potential to receive a broad label. REGENXBIO has recently confirmed with the FDA that the pathway can be used given the ongoing high unmet need for differentiated treatment options in the Duchenne community. RGX-202 is the most advanced gene therapy enrolling in active clinical trials and is anticipated to be the next gene therapy in a BLA filing for Duchenne. "We believe RGX-202 has unique, differentiating features that support its potential to be a best-in-class product and we are pleased to expand its clinical development to reach a wider range of boys with Duchenne in need of treatment options," said Curran Simpson, Chief Operating Officer of REGENXBIO and President and CEO-elect. "Supported by the strong safety pro positive microdystrophin data demonstrated in the AFFINITY DUCHENNE trial, today's news marks significant steps in rapidly accelerating RGX-202 towards pivotal stage and future commercialization." "The Duchenne community remains in need of differentiated treatment options, and I'm pleased to see the expansion of the AFFINITY DUCHENNE trial to evaluate RGX-202 in younger patients," said Vamshi K. Rao, M.D., Lurie Children's Hospital, Associate Professor of Pediatrics, Northwestern University Feinberg School of Medicine and trial investigator. "With the wider adoption of newborn screening, there is now an increased opportunity to treat patients earlier, with the hope of impacting disease and preserving muscle." Clinical Program Updates The Company continues to rapidly enroll the remaining patients in the ages 4-11 cohort (dose level 2 expansion cohort) and expects to imminently complete the enrollment of up to seven patients at dose level 2 early third quarter of 2024. REGENXBIO expects to share initial strength and functional assessment data for both dose levels of the AFFINITY DUCHENNE trial in the second half of 2024. Initiation of the pivotal trial is on track for late third quarter to early fourth quarter of 2024. RGX-202 in the AFFINITY DUCHENNE trial is manufactured using REGENXBIO's proprietary, high-yielding NAVXpress™ platform process. This suspension-based manufacturing process has demonstrated robust scalability with consistent yield and product purity and is ready for product commercialization. As of May 3, 2024, RGX-202 has been well tolerated with no drug-related serious adverse events in five patients, aged 4.4 to 12.1. All five patients who completed three-month trial assessments indicate encouraging increases in expression of RGX-202 microdystrophin and reduction from baseline in serum CK levels, supporting evidence of clinical improvement. AFFINITY DUCHENNE Trial Design The Phase I/II AFFINITY DUCHENNE trial is a multicenter, open-label dose escalation and dose expansion clinical study to evaluate the safety, tolerability and clinical efficacy of a one-time intravenous (IV) dose of RGX-202 in patients with Duchenne aged 1-11. The trial design was informed by the Duchenne community and engagement with key opinion leaders, including a comprehensive, short-term, prophylactic immunosuppression regimen to proactively mitigate potential complement-mediated immunologic responses, and inclusion criteria based on dystrophin gene mutation status, including DMD gene mutations in exons 18 and above. Trial endpoints include safety, immunogenicity assessments, pharmacodynamic and pharmacokinetic measures of RGX-202, including microdystrophin protein levels in muscle, and strength and functional assessments, including the North Star Ambulatory Assessment (NSAA) and timed function tests. About RGX-202 RGX-202 has differentiated and important biology most similar to naturally occurring dystrophin that protects from the muscle degradation associated with Duchenne. RGX-202 is designed with advanced science to deliver a transgene for a novel microdystrophin that includes the functional elements of the C-Terminal (CT) domain found in naturally occurring dystrophin. Presence of the CT domain has been shown in preclinical studies to recruit several key proteins to the muscle cell membrane, leading to improved muscle resistance to contraction-induced muscle damage in dystrophic mice. Additional design features, including codon optimization and reduction of CpG content, may potentially improve gene expression, increase translational efficiency and reduce immunogenicity. RGX-202 is designed to support the delivery and targeted expression of genes throughout skeletal and heart muscle using the NAV AAV8 vector, a vector used in numerous clinical trials, and a well-characterized muscle-specific promoter (Spc5-12). About Duchenne Muscular Dystrophy Duchenne is a severe, progressive, degenerative muscle disease, affecting 1 in 3,500 to 5,000 boys born each year worldwide. Duchenne is caused by mutations in the Duchenne gene which encodes for dystrophin, a protein involved in muscle cell structure and signaling pathways. Without dystrophin, muscles throughout the body degenerate and become weak, eventually leading to loss of movement and independence, required support for breathing, cardiomyopathy and premature death. 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, clinical trials, regulatory plans, costs and cash flow. REGENXBIO has based these forward-looking statements on its current expectations and assumptions and analyses made by REGENXBIO in light of its experience and its perception of historical trends, current conditions and expected future developments, as well as other factors REGENXBIO believes are appropriate under the circumstances. However, whether actual results and developments will conform with REGENXBIO's expectations and predictions is subject to a number of risks and uncertainties, including the timing of enrollment, commencement and completion and the success of clinical trials conducted by REGENXBIO, its licensees and its partners, the timing of commencement and completion and the success of preclinical studies conducted by REGENXBIO and its development partners, the timely development and launch of new products, the ability to obtain and maintain regulatory approval of product candidates, the ability to obtain and maintain intellectual property protection for product candidates and technology, trends and challenges in the business and markets in which REGENXBIO operates, the size and growth of potential markets for product candidates and the ability to serve those markets, the rate and degree of acceptance of product candidates, and other factors, many of which are beyond the control of REGENXBIO. 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

Clinical StudyGene Therapy

18 Jun 2024

·www.biospace.com

REGENXBIO Announces Successful Pre-BLA Meeting with FDA to Support Accelerated Approval Pathway for RGX-121 for the Treatment of MPS II

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. REGENXBIO has based these forward-looking statements on its current expectations and assumptions and analyses made by REGENXBIO in light of its experience and its perception of historical trends, current conditions and expected future developments, as well as other factors REGENXBIO believes are appropriate under the circumstances. However, whether actual results and developments will conform with REGENXBIO's expectations and predictions is subject to a number of risks and uncertainties, including the timing of enrollment, commencement and completion and the success of clinical trials conducted by REGENXBIO, its licensees and its partners, the timing of commencement and completion and the success of preclinical studies conducted by REGENXBIO and its development partners, the timely development and launch of new products, the ability to obtain and maintain regulatory approval of product candidates, the ability to obtain and maintain intellectual property protection for product candidates and technology, trends and challenges in the business and markets in which REGENXBIO operates, the size and growth of potential markets for product candidates and the ability to serve those markets, the rate and degree of acceptance of product candidates, and other factors, many of which are beyond the control of REGENXBIO. 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

Breakthrough TherapyOrphan DrugPriority ReviewFast TrackGene Therapy

12 Jun 2024

·www.globenewswire.com

Clearside Biomedical’s Leadership in Suprachoroidal Delivery Featured in Multiple Presentations at the Clinical Trials at the Summit Meeting

- Broad Use of Suprachoroidal Injection Platform Highlighted Across Retinal Indications - - Robust Safety Profile and Encouraging Efficacy Data Reported Utilizing SCS Microinjector® - ALPHARETTA, Ga., June 12, 2024 (GLOBE NEWSWIRE) -- Clearside Biomedical, Inc. (Nasdaq: CLSD), a biopharmaceutical company revolutionizing the delivery of therapies to the back of the eye through the suprachoroidal space (SCS®), announced today that multiple oral presentations were delivered at the Clinical Trials at the Summit (CTS) Meeting on June 8, 2024 in Park City, Utah. These presentations highlighted the versatility and potential advantages of suprachoroidal administration of therapeutics in treating retinal diseases. “Clearside is leading the way in suprachoroidal delivery, including having the only FDA approved product for suprachoroidal use and a second program with an expected near-term clinical data readout for CLS-AX in the large wet AMD market,” said Victor Chong, M.D., MBA, Chief Medical Officer of Clearside. “We believe that suprachoroidal delivery combined with the differentiated mechanism of action and high potency of axitinib offers the potential for CLS-AX to be a long-term maintenance therapy for wet AMD patients. In addition, our licensing partners continue to report encouraging clinical data from their development programs. Collectively, there are four potential therapies in clinical development with suprachoroidal delivery targeting five different serious opthalmic indications.” Title: Suprachoroidal Drug Delivery in the Real WorldPresented by: Glenn Yiu , M.D., PhDSummary: Suprachoroidal injections are a new and innovative technique that may provide improved bioavailability to the posterior segment of the eye while minimizing exposure and adverse effects on the anterior segment.Real-world data on the use of XIPERE® (triamcinolone acetonide injectable suspension), for the treatment of macular edema associated with uveitis, showed excellent durability in which more than 75% of eyes did not require retreatment for 6 months after a single dose of XIPERE.Suprachoroidal injections can be easily performed in an office-based setting with special considerations that are different from conventional intravitreal injections including needle selection and optimal delivery technique.Potential applications beyond delivering steroids, such as angiogenesis inhibitors and gene therapies, may broaden the scope of suprachoroidal delivery in ophthalmic practice. Title: Update on CLS-AX for nAMDPresented by: Lejla Vajzovic, M.D., FASRSSummary: Clearside is utilizing its patented suprachoroidal injection technology to deliver CLS-AX, a small molecule suspension of the tyrosine kinase inhibitor, axitinib, for the treatment of neovascular age-related macular degeneration (wet AMD).With thousands of suprachoroidal injections performed to date, the safety profile of the SCS Microinjector® is comparable to intravitreal injections.OASIS, the dose ranging Phase 1/2a study of CLS-AX in wet AMD, demonstrated an excellent safety profile, promising durability and biologic effect.ODYSSEY, the 36-week randomized, double-masked Phase 2b clinical trial of CLS-AX in 60 participants with wet AMD, is ongoing with topline data expected in Q3 2024. The ODYSSEY trial is differentiated from other mid-phase wet AMD studies, as it required enrollment of patients with confirmed, active disease and allows re-treatment with CLS-AX to provide multi-dosing data in a chronic disease. Additional Presentations Delivered by Clearside Commercial and Development Partners Partner: REGENXBIOTitle: Suprachoroidal Delivery of Investigational ABBV-RGX-314 Gene Therapy for DR: The Phase 2 ALTITUDE StudyPresented by: Raj Maturi, M.D. Partner: Aura BiosciencesTitle: A New Potential Option for Uveal Melanoma - The Science of Bel-Sar and Phase 3 CoMpass TrialPresented by: Ross Goldstein, M.D., MBA Clearside’s medical meeting presentations can be accessed on the Company’s Publications and Presentations page. About Clearside’s Suprachoroidal Space (SCS®) Injection Platform and SCS Microinjector® Clearside’s patent protected, proprietary suprachoroidal space (SCS®) injection treatment approach offers unprecedented access to the back of the eye, where sight-threatening disease often occurs. The Company’s unique platform is inherently flexible and intended to work with established and new formulations of medications. Clearside’s patented SCS Microinjector® can deliver a wide variety of drug candidates into the suprachoroidal space, providing targeted delivery to potentially improve efficacy and compartmentalization of medication to reduce or eliminate toxic effects on non-diseased cells. The SCS Microinjector system comprises a syringe, a custom-designed hub, and two 30-gauge hollow microneedles of varying lengths, each less than 1.2 millimeters, optimizing insertion and suprachoroidal administration of drugs. About CLS-AX (axitinib injectable suspension) CLS-AX (axitinib injectable suspension) is a proprietary suspension of axitinib for suprachoroidal injection. Axitinib is a tyrosine kinase inhibitor (TKI), currently approved as an oral tablet formulation to treat advanced renal cell carcinoma, that achieves pan-VEGF blockade, directly inhibiting VEGF receptors-1, -2, and -3 with high potency and specificity. Clearside believes this broad VEGF blockade may have efficacy advantages over existing retinal therapies by acting at a different level of the angiogenesis cascade and may benefit patients who sub-optimally respond to current, more narrowly focused anti-VEGF therapies. Suprachoroidal injection of this proprietary suspension of axitinib has demonstrated meaningful potential in preclinical studies in multiple species and in a Phase 1/2a wet AMD clinical trial in which CLS-AX was well tolerated and demonstrated an excellent safety profile. With suprachoroidal administration of axitinib, there is the potential to achieve prolonged duration and targeted delivery to affected tissue layers by compartmentalizing axitinib behind the retina and thereby limiting drug exposure to the front of the eye. Clearside is developing CLS-AX as a long-acting therapy for the treatment of retinal diseases. About Clearside Biomedical, Inc. Clearside Biomedical, Inc. is a biopharmaceutical company revolutionizing the delivery of therapies to the back of the eye through the suprachoroidal space (SCS®). Clearside’s SCS injection platform, utilizing the Company’s patented SCS Microinjector®, enables an in-office, repeatable, non-surgical procedure for the targeted and compartmentalized delivery of a wide variety of therapies to the macula, retina, or choroid to potentially preserve and improve vision in patients with sight-threatening eye diseases. Clearside is developing its own pipeline of small molecule product candidates for administration via its SCS Microinjector. The Company’s lead program, CLS-AX (axitinib injectable suspension), for the treatment of neovascular age-related macular degeneration (wet AMD), is in Phase 2b clinical testing. Clearside developed and gained approval for its first product, XIPERE® (triamcinolone acetonide injectable suspension) for suprachoroidal use, which is available in the U.S. through a commercial partner. Clearside also strategically partners its SCS injection platform with companies utilizing other ophthalmic therapeutic innovations. For more information, please visit clearsidebio.com and follow us on LinkedIn and X. Cautionary Note Regarding Forward-Looking Statements Any statements contained in this press release that do not describe historical facts may constitute forward-looking statements as that term is defined in the Private Securities Litigation Reform Act of 1995. These statements may be identified by words such as “believe”, “expect”, “may”, “plan”, “potential”, “will”, and similar expressions, and are based on Clearside’s current beliefs and expectations. These forward-looking statements include statements regarding the clinical development of CLS-AX and the expected timing of topline results from the ODYSSEY clinical trial as well as the potential benefits of CLS-AX, Clearside’s suprachoroidal delivery technology and Clearside’s SCS Microinjector®. These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements. Risks and uncertainties that may cause actual results to differ materially include uncertainties inherent in the conduct of clinical trials, Clearside’s reliance on third parties over which it may not always have full control and other risks and uncertainties that are described in Clearside’s Annual Report on Form 10-K for the year ended December 31, 2023, filed with the U.S. Securities and Exchange Commission (SEC) on March 12, 2024 and Clearside’s other Periodic Reports filed with the SEC. Any forward-looking statements speak only as of the date of this press release and are based on information available to Clearside as of the date of this release, and Clearside assumes no obligation to, and does not intend to, update any forward-looking statements, whether as a result of new information, future events or otherwise. Source: Clearside Biomedical, Inc.

Clinical ResultPhase 3Phase 2Drug Approval

100 Deals associated with RGX-314

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Glycogen Storage Disease Type II	Phase 3	US	AbbVie, Inc.	28 Dec 2021
Glycogen Storage Disease Type II	Phase 3	CA	AbbVie, Inc.	28 Dec 2021
Glycogen Storage Disease Type II	Phase 3	PR	AbbVie, Inc.	28 Dec 2021
Wet age-related macular degeneration	Phase 3	US	AbbVie, Inc.	28 Dec 2021
Wet age-related macular degeneration	Phase 3	CA	AbbVie, Inc.	28 Dec 2021
Wet age-related macular degeneration	Phase 3	PR	AbbVie, Inc.	28 Dec 2021
Choroidal Neovascularization	Phase 3	US	AbbVie, Inc.	29 Dec 2020
Wet Macular Degeneration	Phase 3	US	AbbVie, Inc.	29 Dec 2020
Diabetic Retinopathy	Phase 2	US	RegenxBio, Inc.	20 Nov 2020

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04514653 (AAVIATE, Corporate Publications) Manual	Phase 2	Wet Macular Degeneration	106	ABBV-RGX-314	izarkmstbd(zntduvladc) = in the study eye were mild or moderate and included conjunctival hemorrhage, increased intraocular pressure, episcleritis, and conjunctival hyperemia. lzuzvyscuu (yaxyxzwiaj ) View more	Positive	16 Jan 2024
Phase I/IIa (ARVO2023)	Phase 1/2	Wet age-related macular degeneration	42	RGX-314	dtvniqpilx(tnfkaoukah) = no new drug-related ocular adverse events reported in Cohorts 1-4 and one drug-related adverse event of significantly decreased BCVA in Cohort 5 gptpsivjss (bcptfurwff )	Positive	23 Apr 2023
NCT04567550 (ALTITUDE, Corporate Publications) Manual	Phase 2	Diabetic Retinopathy	60	RGX-314	cuollsxhfi(pwjfangabq) = pdycmckgpc pyyexekrwe (csxvnhcupf ) View more	Positive	02 Nov 2022
NCT04567550 (ALTITUDE, Corporate Publications) Manual	Phase 2	Diabetic Retinopathy	60	control	cuollsxhfi(pwjfangabq) = oppjhwquso pyyexekrwe (csxvnhcupf ) View more	Positive	02 Nov 2022
NCT04567550 (ALTITUDE, Corporate Publications) Manual	Phase 2	Diabetic Retinopathy	20	RGX-314	nvknzizyaw(adkfbbcufo) = kypwweghxh kwexhycunh (pqsbzwrpnt ) View more	Positive	13 Sep 2022
NCT04567550 (ALTITUDE, Corporate Publications) Manual	Phase 2	Diabetic Retinopathy	20	Observational	nvknzizyaw(adkfbbcufo) = wasppkeosz kwexhycunh (pqsbzwrpnt ) View more	Positive	13 Sep 2022
NCT04514653 (AAVIATE, PRNewswire) Manual	Phase 2	Wet age-related macular degeneration	19	RGX-314	wnocwrmcdb(hrzjdpaaka) = fhmftbhbiy zhcmulavbm (uonxmmqfsi ) View more	Positive	01 Oct 2021
NCT04514653 (AAVIATE, PRNewswire) Manual	Phase 2	Wet age-related macular degeneration	19	Ranibizumab	wnocwrmcdb(hrzjdpaaka) = wdunntueut zhcmulavbm (uonxmmqfsi ) View more	Positive	01 Oct 2021
RGX-314 (ASGCT2020)	Phase 1/2	Wet age-related macular degeneration	42	RGX-314 gene therapy	tyounsdkrl(fiiddncbku) = improved central retinal thickness (-83 µm) vwuzghnsps (efapbibqkk ) View more	Positive	28 Apr 2020

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