rebisufligene etisparvovec (UX111) / Abeona Therap, Ultragenyx - LARVOL DELTA

Treatment with UX111 Gene Therapy Rapidly Reduced Heparan Sulfate (HS) Exposure in Cerebrospinal Fluid (CSF) and Improved Long-term Cognitive Function in Children with Mucopolysaccharidosis IIIA (MPS IIIA) (AAN 2025) - P1/2, P3 | "UX111 appears safe and effective in children with MPS IIIA leading to reduced CSF HS exposure and improved cognitive function."

Clinical • Gene therapy • CNS Disorders • Gene Therapies • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

Ultragenyx Announces FDA Acceptance and Priority Review of the Biologics License Application (BLA) for UX111 AAV Gene Therapy to Treat Sanfilippo Syndrome Type A (MPS IIIA) (GlobeNewswire) - "Ultragenyx Pharmaceutical...announced the U.S. Food and Drug Administration (FDA or the Agency) has accepted for review the Biologics License Application (BLA) seeking accelerated approval for UX111 (ABO-102) AAV gene therapy as a treatment for patients with Sanfilippo syndrome type A (MPS IIIA). The FDA granted the BLA Priority Review with a Prescription Drug User Fee Act (PDUFA) action date of August 18, 2025. The FDA also informed the company that they are not currently planning to hold an advisory committee meeting to discuss this application....The BLA submission for UX111 is supported by available data, including the latest data from the ongoing pivotal Transpher A and long-term follow-up studies presented at WORLDSymposium 2025..."

FDA filing • PDUFA • Priority review • Lysosomal Storage Diseases

Phase I/II/III Gene Transfer Clinical Trial of ScAAV9.U1a.hSGSH (clinicaltrials.gov) - P2/3 | N=36 | Recruiting | Sponsor: Ultragenyx Pharmaceutical Inc | Active, not recruiting ➔ Recruiting

Enrollment open • Gene Therapies • Hunter Syndrome • Lysosomal Storage Diseases

Phase I/II/III Gene Transfer Clinical Trial of scAAV9.U1a.hSGSH (clinicaltrials.gov) - P2/3 | N=36 | Active, not recruiting | Sponsor: Ultragenyx Pharmaceutical Inc | Trial completion date: Jan 2025 ➔ Jul 2027 | Trial primary completion date: Jan 2025 ➔ Jul 2027

Trial completion date • Trial primary completion date • Gene Therapies • Hunter Syndrome • Lysosomal Storage Diseases

Phase I/II/III Gene Transfer Clinical Trial of scAAV9.U1a.hSGSH (clinicaltrials.gov) - P2/3 | N=28 | Active, not recruiting | Sponsor: Ultragenyx Pharmaceutical Inc | Trial completion date: Jun 2024 ➔ Jan 2025 | Trial primary completion date: Jun 2024 ➔ Jan 2025

Trial completion date • Trial primary completion date • Gene Therapies • Hunter Syndrome • Lysosomal Storage Diseases

An Integrated Process Characterization Approach to Enable Accelerated Commercialization Timeline of an Adeno-Associated Virus Based Treatment for Sanfilippo Syndrome (ASGCT 2024) - "Specifically, UX111 historical manufacturing data, UX111-specific PC data, and rAAV platform PC data are leveraged to generate the process and analytical control strategy (PACS) and to define PPQ ranges. The integrated PC approach not only provided a solid foundation to design a robust and reliable process, but also may enable the timely delivery of drug product to Sanfilippo syndrome patients in need."

Gene Therapies • Hunter Syndrome • Lysosomal Storage Diseases • Rare Diseases

A Long-term Follow-up Study of Patients With MPS IIIA Treated With ABO-102 (clinicaltrials.gov) - P3 | N=33 | Enrolling by invitation | Sponsor: Ultragenyx Pharmaceutical Inc | Phase classification: P=N/A ➔ P3 | N=50 ➔ 33 | Trial completion date: Dec 2026 ➔ Jun 2027

Enrollment change • Phase classification • Trial completion date • Gene Therapies • Hunter Syndrome • Lysosomal Storage Diseases

Phase I/II/III Gene Transfer Clinical Trial of scAAV9.U1a.hSGSH (clinicaltrials.gov) - P2/3 | N=28 | Active, not recruiting | Sponsor: Ultragenyx Pharmaceutical Inc | Phase classification: P1/2 ➔ P2/3 | Trial completion date: Dec 2024 ➔ Jun 2024 | Trial primary completion date: Dec 2024 ➔ Jun 2024

Phase classification • Trial completion date • Trial primary completion date • Gene Therapies • Hunter Syndrome • Lysosomal Storage Diseases

Phase I/II/III Gene Transfer Clinical Trial of scAAV9.U1a.hSGSH (clinicaltrials.gov) - P1/2 | N=28 | Active, not recruiting | Sponsor: Ultragenyx Pharmaceutical Inc | Recruiting ➔ Active, not recruiting

Enrollment closed • Gene Therapies • Hunter Syndrome • Lysosomal Storage Diseases

A Long-term Follow-up Study of Patients With MPS IIIA Treated With ABO-102 (clinicaltrials.gov) - P=N/A | N=50 | Enrolling by invitation | Sponsor: Ultragenyx Pharmaceutical Inc | Recruiting ➔ Enrolling by invitation

Enrollment status • Gene Therapies • Hunter Syndrome • Lysosomal Storage Diseases

Updated Interim Results of Transpher A, a Multicenter, Single-Dose, Pivotal Clinical Trial of ABO-102 Gene Therapy for Sanfilippo Syndrome Type A (Mucopolysaccharidosis IIIA) (ASGCT 2022) - P=N/A, P1/2 | "Investigational ABO-102 gene therapy in the youngest patients treated before advanced neurodegeneration (<2 years old or DQ ≥ 60) in Cohort 3 is associated with overall improvements in neurocognitive assessments, behavioral domains, biomarkers, and physiological volumetric changes that typically progressively decline in MPS IIIA without treatment or at subtherapeutic doses (Cohorts 1 and 2). Collectively, these data demonstrate the potential for investigational ABO-102 gene therapy to address a high unmet treatment need for patients with MPS IIIA and their caregivers."

Clinical • CNS Disorders • Gene Therapies • Hepatology • Lysosomal Storage Diseases

Gene Transfer Study of ABO-102 in Patients With Middle and Advanced Phases of MPS IIIA Disease (clinicaltrials.gov) - P1/2 | N=5 | Terminated | Sponsor: Abeona Therapeutics, Inc | N=12 ➔ 5 | Trial completion date: Dec 2023 ➔ Mar 2022 | Recruiting ➔ Terminated | Trial primary completion date: Dec 2023 ➔ Mar 2022; Terminated due to lack of efficacy seen in patients with advanced MPS IIIA disease. The patients will be followed up annually for safety until five years post dosing

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Gene Therapies • Hunter Syndrome • Lysosomal Storage Diseases

Updated results of Transpher A, a multicenter, single-dose, Phase 1/2 clinical trial of ABO-102 investigational gene therapy for Sanfilippo syndrome type A (mucopolysaccharidosis IIIA) (AAN 2022) - P1/2 | "Investigational ABO-102 in patients with MPS IIIA showed a favorable long-term safety profile and led to significant reductions in central nervous system and systemic biomarkers (Cohort 3), with clear indications of meaningful neurocognitive benefit in the youngest patients treated before advanced neurodegeneration."

Clinical • P1/2 data • CNS Disorders • Gene Therapies • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

Phase I/II Gene Transfer Clinical Trial of scAAV9.U1a.hSGSH (clinicaltrials.gov) - P1/2; N=22; Recruiting; Sponsor: Abeona Therapeutics, Inc; Trial completion date: Dec 2022 ➔ Dec 2024; Trial primary completion date: Dec 2022 ➔ Dec 2024

Trial completion date • Trial primary completion date • Gene Therapies • Hunter Syndrome • Lysosomal Storage Diseases • MRI

A Long-term Follow-up Study of Patients With MPS IIIA Treated With ABO-102 (clinicaltrials.gov) - P=N/A; N=50; Recruiting; Sponsor: Abeona Therapeutics, Inc; Trial completion date: Dec 2025 ➔ Dec 2026; Trial primary completion date: Dec 2025 ➔ Dec 2026

Trial completion date • Trial primary completion date • Gene Therapies • Hunter Syndrome • Lysosomal Storage Diseases

[VIRTUAL] Updated results of Transpher A, a multicentre, single-dose, Phase 1/2 clinical trial of ABO-102 investigational gene therapy for Sanfilippo syndrome type A (mucopolysaccharidosis IIIA) (ESGCT 2021) - No abstract available

Clinical • P1/2 data • Gene Therapies • Lysosomal Storage Diseases

[VIRTUAL] Updated Results of Transpher A, a Multicenter, Single-Dose, Phase 1/2 Clinical Trial of ABO-102 Gene Therapy for Sanfilippo Syndrome Type A (Mucopolysaccharidosis IIIA) (ASGCT 2021) - "Neurocognitive evaluation showed continuous gain of cognitive skills in younger patients (≤30 months, DQ>60) in Cohort 3, with a follow-up of 18-36 months, well beyond the point where natural history reports relentless neurodegeneration. Overall, intravenous administration of ABO-102 in MPS-IIIA patients showed a favorable long-term safety profile and led to statistically significant reductions in CNS and systemic biomarkers, with clear indications of meaningful neurocognitive benefit in the youngest patients treated with 3x1013 vg/kg, before advanced neurodegeneration."

Clinical • P1/2 data • CNS Disorders • Gene Therapies • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

Systemic scAAV9.U1a.hSGSH delivery corrects brain biochemistry in mucopolysaccharidosis type IIIA at early and later stages of disease. (PubMed, Hum Gene Ther) - "In order to assess the efficacy of restoring the underlying biochemistry in the MPS IIIA brain, tail vein injections of self-complementary AAV9 human N-sulphoglucosamine sulphohydrolase (scAAV9.U1A.hSGSH) at 3 x 1013 vg/kg were administered to 6 and 16 week old MPS IIIA mice. These results demonstrate that the gene product is actively clearing primary heparan sulphate and secondary ganglioside accumulation in MPS IIIA mice but in older mice, neurocognitive impairments remain. This is likely due to secondary downstream consequences of heparan sulphate affecting neurological functions that are not reversible upon substrate clearance."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Gene Therapies • Hunter Syndrome

A Long-term Follow-up Study of Patients With MPS IIIA Treated With ABO-102 (clinicaltrials.gov) - P=N/A; N=50; Recruiting; Sponsor: Abeona Therapeutics, Inc; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Gene Therapies • Hunter Syndrome

A Long-term Follow-up Study of Patients With MPS IIIA Treated With ABO-102 (clinicaltrials.gov) - P=N/A; N=50; Not yet recruiting; Sponsor: Abeona Therapeutics, Inc; Initiation date: May 2020 ➔ Sep 2020

Clinical • Trial initiation date • Gene Therapies • Hunter Syndrome

Gene Transfer Study of ABO-102 in Patients With Middle and Advanced Phases of MPS IIIA Disease (clinicaltrials.gov) - P1/2; N=12; Recruiting; Sponsor: Abeona Therapeutics, Inc; Trial completion date: Dec 2022 ➔ Dec 2023; Trial primary completion date: Dec 2022 ➔ Dec 2023

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

A Long-term Follow-up Study of Patients with MPS IIIA from Gene Therapy Clinical Trials Involving the Administration of ABO-102 (scAAV9.U1a.hSGSH) Estudio de seguimiento a largo plazo de pacientes con MPS IIIA procedentes de ensayos clínicos de terapia génica que incluyen la administración de ABO-102 (scAAV9.U1a.hSGSH) (clinicaltrialsregister.eu) - P1/2; N=34; Ongoing; Sponsor: Abeona Therapeutics Inc

Clinical • New P1/2 trial • Gene Therapies • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

A Long-term Follow-up Study of Patients With MPS IIIA Treated With ABO-102 (clinicaltrials.gov) - P; N=50; Not yet recruiting; Sponsor: Abeona Therapeutics, Inc

Clinical • New trial • Gene Therapies • Genetic Disorders

".@AbeonaBio receives @EMA_News PRIME designation for ABO-102 for the treatment of Sanfilippo syndrome type A #GlobalDataLeadTweet" (@PharmSource)

Clinical

Gene Transfer Study of ABO-102 in Patients With Middle and Advanced Phases of MPS IIIA Disease (clinicaltrials.gov) - P1/2; N=12; Recruiting; Sponsor: Abeona Therapeutics, Inc; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open