clemidsogene lanparvovec (RGX-121) / REGENXBIO, Nippon Shinyaku - LARVOL DELTA

REGENXBIO…announced that the U.S. Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) regarding its Biologics License Application (BLA) for RGX-121 (clemidsogene lanparvovec) for the treatment of Mucopolysaccharidosis II (MPS II), an ultra-rare neurodegenerative disease also known as Hunter syndrome (PRNewswire) - "In the February 7, 2026 CRL, the FDA stated 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....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, all of which would be challenging in an ultra-rare disease population, like MPS II....REGENXBIO plans to request a Type A meeting to discuss the CRL, as well as the planned BLA resubmission..."

CRL • Hunter Syndrome

RGX-121-3102 Gene Therapy in Participants With MPS II (Hunter Syndrome) (clinicaltrials.gov) - P3 | N=2 | Recruiting | Sponsor: REGENXBIO Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Gene Therapies • Hunter Syndrome • Pediatrics

RGX-121-3102 Gene Therapy in Participants With MPS II (Hunter Syndrome) (clinicaltrials.gov) - P3 | N=2 | Not yet recruiting | Sponsor: REGENXBIO Inc.

New P3 trial • Gene Therapies • Hunter Syndrome • Pediatrics

Daily Living Skills on the Vineland Adaptive Behavioral Scale Version 2 (VABS-II) in Neuronopathic Mucopolysaccharidosis Type II (MPS II) (SSIEM 2023) - P2/3 | "RGX-121 has the potential to provide sustained skill acquisition in daily living domains that are applicable to young children with neuronopathic MPS II."

Hunter Syndrome • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

RGX-121 An investigational gene therapy for the treatment of neuronopathic mucopolysaccharidosis type II (MPS II), an interim analysis of data from the first-in-human study (SSIEM 2023) - P2/3 | "RGX-121 has the potential to provide sustained CNS clinical outcomes and additional systemic effects in MPS II patients."

First-in-human • Gene therapy • P1 data • Gene Therapies • Hunter Syndrome • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

REGENXBIO Announces FDA Review Extension of BLA for RGX-121 to Treat Patients with MPS II (PRNewswire) - "The Prescription Drug User Fee Act (PDUFA) goal date has been extended from November 9, 2025 to February 8, 2026. The extension follows the Company's submission of longer-term clinical data for all patients in the pivotal study of RGX-121 (n=13)....REGENXBIO plans to present updated pivotal data during the ICIEM meeting in September 2025."

Clinical data • PDUFA • Hunter Syndrome

RGX-121 (clemidsogene lanparvovec) : an investigational AAV Gene Therapy for the Treatment of Neuronopathic Mucopolysaccharidosis Type II (ASGCT 2025) - P2/3 | "We will discuss the outcome of CAMPSIITE™, a phase I/II/III, open-label trial involving 25 nMPS II patients treated with RGX-121 (NCT03566043). Having completed this initial clinical study, we are currently seeking commercial authorization using the accelerated approval pathway."

Gene therapy • CNS Disorders • Gene Therapies • Hunter Syndrome • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

REGENXBIO Announces FDA Acceptance and Priority Review of the BLA for RGX-121 for MPS II (GlobeNewswire) - "REGENXBIO Inc...today announced the U.S. Food and Drug Administration (FDA) has accepted for review the Biologics License Application (BLA) seeking accelerated approval for clemidsogene lanparvovec (RGX-121) for the treatment of Mucopolysaccharidosis II (MPS II), also known as Hunter syndrome....The FDA granted the BLA Priority Review with a Prescription Drug User Fee Act (PDUFA) target action date of November 9, 2025."

FDA filing • PDUFA • Priority review • Hunter Syndrome

REGENXBIO Announces Closing of Strategic Partnership with Nippon Shinyaku for MPS Diseases (PRNewswire) - "REGENXBIO Inc...today announced the closing of its previously announced strategic partnership with Nippon Shinyaku....Under the terms of the agreement, REGENXBIO and Nippon Shinyaku will develop and commercialize RGX-121 (clemidsogene lanparvovec) for Mucopolysaccharidosis II (MPS II), also known as Hunter syndrome and RGX-111 for Mucopolysaccharidosis I (MPS I), also known as Hurler syndrome in the United States and Asia."

Licensing / partnership • Hunter Syndrome

RGX-121 Gene Therapy in Children 5 Years of Age and Over With MPS II (Hunter Syndrome) (clinicaltrials.gov) - P1/2 | N=6 | Completed | Sponsor: REGENXBIO Inc. | Active, not recruiting ➔ Completed | Trial completion date: Nov 2025 ➔ May 2024

Trial completion • Trial completion date • Gene Therapies • Hunter Syndrome

CAMPSIITE™ RGX-121 Gene Therapy in Subjects With MPS II (Hunter Syndrome) (clinicaltrials.gov) - P2/3 | N=48 | Active, not recruiting | Sponsor: REGENXBIO Inc. | Trial completion date: May 2025 ➔ Aug 2025

Trial completion date • Gene Therapies • Hunter Syndrome • Pediatrics

REGENXBIO and Nippon Shinyaku Announce Exclusive Partnership to Develop and Commercialize RGX-121 and RGX-111 for MPS Diseases (PRNewswire) - "REGENXBIO Inc...and Nippon Shinyaku Co., Ltd...announced a strategic partnership for the development and commercialization of RGX-121 for the treatment of Mucopolysaccharidosis II (MPS II), also known as Hunter syndrome, and RGX-111 for Mucopolysaccharidosis I (MPS I), also known as Hurler syndrome. Under the terms of the agreement, REGENXBIO will receive $110 million at closing and up to an additional $700 million if certain milestones are achieved, consisting of $40 million in potential development and regulatory milestones and $660 million in potential sales milestones. REGENXBIO will also receive meaningful double-digit royalties on net sales in the U.S. and Asia (collectively, the 'Licensed Territory')....REGENXBIO retains rights to RGX-121 Priority Review Voucher (PRV) with potential accelerated approval expected in 2025; rolling BLA submission underway."

FDA approval • Licensing / partnership • Hunter Syndrome • Hurler Syndrome

CAMPSIITE™ PHASE I/II/III: AN INTERIM CLINICAL STUDY UPDATE OF RGX-121, AN INVESTIGATIONAL GENE THERAPY FOR THE TREATMENT OF NEURONOPATHIC MUCOPOLYSACCHARIDOSIS TYPE II (MPS II) (SSIEM 2024) - P2/3 | "RGX-121 has the potential to provide sustained CNS clinical outcomes and additional systemic effects in MPS II patients."

Clinical • Gene therapy • P1/2 data • Gene Therapies • Hunter Syndrome • Rare Diseases

CAMPSIITE™ PHASE I/II/III: AN INTERIM CLINICAL STUDY UPDATE OF RGX-121, AN INVESTIGATIONAL GENE THERAPY FOR THE TREATMENT OF NEURONOPATHIC MUCOPOLYSACCHARIDOSIS TYPE II (MPS II) (SSIEM 2024) - P2/3 | "RGX-121 has the potential to provide sustained CNS clinical outcomes and additional systemic effects in MPS II patients."

Clinical • Gene therapy • P1/2 data • Gene Therapies • Hunter Syndrome • Rare Diseases

CAMPSIITE™ Phase I/II/III: An Interim Clinical Study Update of RGX-121, an Investigational Gene Therapy for the Treatment of Neuronopathic Mucopolysaccharidosis Type II (MPS II) (ASGCT 2024) - P2/3 | "RGX-121 has the potential to provide sustained CNS clinical outcomes and additional systemic effects in MPS II patients."

Clinical • Gene therapy • P1/2 data • Gene Therapies • Hunter Syndrome • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

CAMPSIITE™ Phase I/II/III: An interim clinical study update of RGX-121, an investigational gene therapy for the treatment of neuronopathic mucopolysaccharidosis type II (MPS II) (SIMD 2024) - P2/3 | "RGX-121 has the potential to provide sustained CNS clinical outcomes and additional systemic effects in MPS II patients."

Clinical • Gene therapy • P1/2 data • Gene Therapies • Hunter Syndrome • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

Comparative dose effectiveness of intravenous and intrathecal AAV9.CB7.hIDS, RGX-121, in mucopolysaccharidosis type II mice. (PubMed, Mol Ther Methods Clin Dev) - "In the brain, a dose of 1 × 1011 gc i.t. achieved the highest IDS activity levels and the greatest reduction in GAG content, and it prevented neurocognitive deficiency. We conclude that a dose of 1 × 1010 gc normalized metabolic and skeletal outcomes, while neurologic improvement required a dose of 1 × 1011 gc, thereby suggesting the prospect of a similar direct benefit in humans."

Journal • Preclinical • CNS Disorders • Gene Therapies • Hunter Syndrome • Rare Diseases

RGX-121: AN INVESTIGATIONAL GENE THERAPY FOR THE TREATMENT OF NEURONOPATHIC MUCOPOLYSACCHARIDOSIS TYPE II (MPS II): INTERIM ANALYSIS OF DATA FROM THE FIRST-IN-HUMAN STUDY (WRMC 2024) - P2/3 | "RGX-121 has the potential to provide sustained CNS clinical outcomes and additional systemic effects in MPS II patients."

Gene therapy • P1 data • Gene Therapies • Hunter Syndrome • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

CAMPSIITE™ RGX-121 Gene Therapy in Subjects With MPS II (Hunter Syndrome) (clinicaltrials.gov) - P2/3 | N=48 | Active, not recruiting | Sponsor: REGENXBIO Inc.

Gene therapy • Trial completion date • Trial primary completion date • Gene Therapies • Hunter Syndrome • Pediatrics

RGX-121 Gene Therapy in Children 5 Years of Age and Over With MPS II (Hunter Syndrome) (clinicaltrials.gov) - P1/2 | N=6 | Active, not recruiting | Sponsor: REGENXBIO Inc.

Gene therapy • Trial completion date • Trial primary completion date • Gene Therapies • Hunter Syndrome

CAMPSIITE™ RGX-121 Gene Therapy in Subjects With MPS II (Hunter Syndrome) (clinicaltrials.gov) - P2/3 | N=48 | Active, not recruiting | Sponsor: REGENXBIO Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Gene therapy • Gene Therapies • Hunter Syndrome • Pediatrics

REGENXBIO Announces Presentations at the Society for the Study of Inborn Errors of Metabolism Annual Symposium 2023 (PRNewswire) - "REGENXBIO...announced presentations at the Society for the Study of Inborn Errors of Metabolism Annual Symposium 2023 in Jerusalem, Israel (August 29 – September 1). Investigators will deliver encore presentations of interim clinical trial data from REGENXBIO's pipeline of one-time investigational AAV Therapeutics for progressive, neurodegenerative lysosomal storage disorders, as well as initial interim data from the single-patient, investigator-initiated study of RGX-181 for the treatment of CLN2 disease."

Clinical data • CNS Disorders • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders

RGX-121 Gene Therapy for the Treatment of Neuronopathic Mucopolysaccharidosis Type II (MPS II): Interim Analysis of Data from the First in Human Study (ASGCT 2023) - P2/3 | "Updated interim results from this trial will be presented. RGX-121 has the potential to provide sustained CNS clinical outcomes and additional systemic effects in MPS II patients."

Gene therapy • P1 data • Gene Therapies • Hunter Syndrome • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

RGX-121 Gene Therapy in Children 5 Years of Age and Over With MPS II (Hunter Syndrome) (clinicaltrials.gov) - P1/2 | N=6 | Active, not recruiting | Sponsor: REGENXBIO Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Gene therapy • Gene Therapies • Hunter Syndrome

RGX-121 Gene Therapy in Children 5 Years of Age and Over With MPS II (Hunter Syndrome) (clinicaltrials.gov) - P1/2 | N=6 | Recruiting | Sponsor: REGENXBIO Inc. | Trial primary completion date: Jun 2022 ➔ May 2023

Trial primary completion date • Gene Therapies • Hunter Syndrome