LYS-SAF302 / Lysogene, Sarepta Therap - LARVOL DELTA

Longitudinal changes of Anti-AAV9 and Anti-AAVrh74 antibodies in treated and untreated patients (MDA 2024) - "Subjects received SGT-001 (N=7), Zolgensma (N=7), PF-06939926 (N=2), AT132 (N=1), LYS-SAF302 (N=1), PGTC PD-AAV004 (N=2), all AAV9 products... 169 untreated subjects (115 male) with 1 plasma/serum sample for analysis were included. Median age was 13 (3-37). Of these, 92 (54%) were seropositive for Anti-AAV9 IgG at initial collection."

Clinical • CNS Disorders • Gene Therapies • Immunology

Focal lesions following intracerebral gene therapy for mucopolysaccharidosis IIIA. (PubMed, Ann Clin Transl Neurol) - "Results suggest that intracerebral gene therapy with local sulfamidase overexpression leads to dysfunction of transduced cells close to injection sites, with extracellular spilling of lysosomal enzymes. This alters extracellular matrix composition, depletes heparan sulfate, impairs astrocyte and oligodendrocyte function, and causes cystic white matter degeneration at the site of highest gene expression. The AAVance trial results will reveal the potential benefit-risk ratio of this therapy."

Gene therapy • Journal • Gene Therapies • Hunter Syndrome • Lysosomal Storage Diseases • Solid Tumor

Update on AAVance, a Phase 2/3 Clinical Trial of LYS-SAF302 Gene Therapy in Children with MPS IIIA (ESGCT 2022) - No abstract available

Clinical • P2/3 data • Gene Therapies • Lysosomal Storage Diseases

An Update on LYS-SAF302 Gene Therapy Study (AAVance) in Children with Mucopolysaccharidosis Type IIIA (ASGCT 2022) - P2/3 | "Safety, tolerability, biomarkers, effect on behavior, sleep and quality of life are secondary endpoints. An update on the status of the study will be presented."

Clinical • CNS Disorders • Gene Therapies • Hunter Syndrome • Lysosomal Storage Diseases

"Lysogene Reports Positive Biomarker Data With LYS-SAF302 https://t.co/6LNxZ7uF8Y" (@NewsFromBW)

Biomarker

Study of AAVrh10-h.SGSH Gene Therapy in Patients With Mucopolysaccharidosis Type IIIA (MPS IIIA) (clinicaltrials.gov) - P2/3; N=20; Active, not recruiting; Sponsor: LYSOGENE; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Gene Therapies • MRI

An Open-Label study with only one arm of treatment that will be carried out in different international sites of Intracerebral Administration of study drug for the Treatment of Sanfilippo syndrome type A (clinicaltrialsregister.eu) - P2/3; N=20; Sponsor: Lysogene SA

New P2/3 trial • Biosimilar • Gene Therapies • Metabolic Disorders

Sarepta Therapeutics Announces First Quarter 2020 Financial Results and Recent Corporate Developments (GlobeNewswire, Sarepta Therapeutics, Inc.) - "$43.3 million increase in clinical and manufacturing expenses primarily due to a continuing ramp-up of the Company’s micro-dystrophin program and the Company’s ESSENCE program. The increases were offset by a ramp-down of the PROMOVI trial in EXONDYS 51 and the Phase 1/2 trial in golodirsen...$2.4 million increase in collaboration cost sharing with Genethon on its micro-dystrophin drug candidates and Lysogene S.A on its MPS IIIA drug candidates."

Commercial • Duchenne Muscular Dystrophy • Genetic Disorders • Infectious Disease • Muscular Dystrophy

An improved AAV vector for neurological correction of the mouse model of Mucopolysaccharidosis IIIA. (PubMed, Hum Gene Ther) - "Following preclinical evaluation in MPSIIIA mice, an adeno-associated virus vector of serotype rh10 designed to deliver SGSH and sulfatase modifying factor 1 (SAF301) was trialed in four MPSIIIA patients, showing good tolerance and absence of adverse events with some improvements in neurocognitive measures. Biodistribution of SAF302 was further assessed using GFP (SAF302GFP), indicating that vector spread was limited to the area around the injection tract. Further modification of the injection strategy to a single depth with higher injection volume increased vector distribution leading to more widespread GFP distribution and sustained expression, suggesting this approach should be adopted in future trials."

Journal • Preclinical

"Lysogene Receives FDA Fast Track Designation for LYS-SAF302 Gene Therapy in MPS IIIA https://t.co/BsrsZKF1wp" (@NewsFromBW)

Fast track designation

AAVrh10 Vector Corrects Disease Pathology in MPS IIIA Mice and Achieves Widespread Distribution of SGSH in Large Animal Brains. (PubMed, Mol Ther Methods Clin Dev) - "The ability of the vector adeno-associated virus (AAV)rh.10-CAG-SGSH (LYS-SAF302) to correct disease pathology was evaluated in a mouse model for MPS IIIA...Increases of SGSH enzyme activity of at least 20% above endogenous levels were detected in 78% (dogs 4 weeks after injection) and 97% (monkeys 6 weeks after injection) of the total brain volume. Taken together, these data validate intraparenchymal AAV administration as a promising method to achieve widespread enzyme distribution and correction of disease pathology in MPS IIIA."

Journal • Preclinical

"Lysogene $LYS 25m€ in cash & cash equivalent at the end of 2018 after Sarepta $SRPT's upfront (last year's deal for LYS-SAF-302 in MPS IIIA), 24m€ net cash position, mkt cap 24m€, EV... 0 Welcome in Europe." (@BiotechRadar)