Lysogene reported positive biomarker data from the ongoing AAVance clinical trial with LYS-SAF302 for the treatment of MPS IIIA (NCT03612869) as well as favorable safety data from the ongoing adaptative clinical trial with LYS-GM101 for the treatment of GM1 gangliosidosis (NCT04273269). LYS-SAF302 biomarker data: Analysis of heparan sulfate (HS) concentration, the primary disease biomarker in MPS IIIA, in the CSF of all 16 patients analyzed at 6 and 12 months after treatment with LYS-SAF302 in AAVance showed 23% reductions relative to pre-treatment values. Furthermore, about 30% reductions in the concentration of secondary storage products GM2 and GM3 ganglioside, which are thought to be possible contributors to neuronal damage in lysosomal storage diseases, were observed in the CSF of treated patients at 12 months after treatment, relative to pre-treatment values.

These results are consistent with the assumption that intraparenchymally administered LYS-SAF302 leads to a specific reduction of heparan sulfate and gangliosides entering the CSF from the brain parenchyma, with no effect on biomarkers entering the CSF from sources other than the brain, such as the spinal cord, choroid plexus or blood. Serum concentrations of the axonal damage biomarker neurofilament light (NF-L) were increased in patients with MPS IIIA at baseline, relative to published values in children with no neurological disease, likely reflecting ongoing neurodegeneration associated with MPS IIIA. Following treatment with LYS-SAF302 in AAVance, mean serum NF-L concentrations increased, reaching about 2-fold above baseline at 6 months.

This increase could be due to either disease progression or transient neuronal damage induced by intracranial surgery, as reported in other clinical trials with different drug products. At 12 months, mean NF-L levels returned to baseline values and then decreased to about 2-fold below baseline values at 18 and 24 months. A decrease of NF-L below baseline levels may indicate a positive effect of treatment.

LYS-GM101 safety data: The P1-GM-101 (NCT04273269) adaptive design gene therapy trial assessing safety and efficacy of intracisternal administration of LYS-GM101, an AAVrh10 vector carrying the GLB1 cDNA, in children with infantile GM1 gangliosidosis is ongoing. No adverse events linked to the intra-cisternal route of administration or the investigational gene therapy have been observed at more than 5 months post-dosing in the first two patients with late infantile GM1 gangliosidosis who have been treated. Based on a review of the initial safety data from these 2 subjects by the study Data Safety Monitoring Board, it has been decided that 2 subjects with early infantile GM1 gangliosidosis would receive LYS-GM101 in early 2022 to complete Stage 1. Consequently, the 3rd patient was treated in early February 2022.

The enrollment of the 4th patient of the safety cohort is ongoing, following which Lysogene will initiate the treatment of the 12 patients of the efficacy confirmatory cohort.