- Evidence of positive biological response to LYS-SAF302 in patients treated in the AAVance clinical trial
- ~30% decrease in pathological heparan sulfate in cerebrospinal fluid 12 months after treatment
- ~40% decrease in pathological GM2 and GM3 gangliosides in cerebrospinal fluid 12 months after treatment
Paris, France — 15 February 2021 at 08:00 am CET — Lysogene (FR0013233475 – LYS), a phase 3 gene therapy platform company targeting central nervous system (CNS) diseases, today reports biomarker data from the ongoing AAVance clinical trial with LYS-SAF302 for the treatment of MPS IIIA (NCT03612869) presented at the WORLDSymposium™ 2021 by Dr. Michaël Hocquemiller, Head of Non-Clinical Development, during the Late-Breaking Science session held on Friday, February 12, 2021.
Concentration of heparan sulfate (HS) in the cerebrospinal fluid (CSF) has been analyzed in 9 patients so far, with samples at baseline (n=9), 6 months (n=8) and 12 months (n=5) after LYS-SAF302 administration. The concentration of abnormally elevated HS-derived oligosaccharides in the CSF was reduced from baseline by 27% and 30% at 6 and 12 months, respectively (p<0.005 and p<0.05 by paired t-test vs baseline, respectively).
In contrast, changes in HS concentrations in serum samples from the same patients were not statistically significant, confirming that the reduction of HS in CSF after LYS-SAF302 treatment is linked to a reduction of HS entering the CSF from the brain parenchyma and not an indirect consequence of a reduction of HS entering the CSF from extra-parenchymal sources, such as choroid plexus or blood. Additionally, changes in dermatan sulfate (DS) and keratan sulfate (KS), which do not accumulate in MPS IIIA, were not statistically significant in serum and CSF, confirming the specificity of HS accumulation in the CSF.
Furthermore, the concentration of abnormally elevated GM2 ganglioside in CSF of the same patients was reduced from baseline by 7% and 40% at 6 and 12 months, respectively (p<0.005 by paired t-test vs baseline at 12 months), while the concentration of abnormally elevated GM3 ganglioside in CSF was reduced from baseline by 7% and 37% at 6 and 12 months, respectively (p<0.005 by paired t-test vs baseline at 12 months).
Ralph Laufer, Chief Scientific Officer at Lysogene said: “The CNS-specific reduction of the disease biomarker HS is consistent with the mode of drug administration, directly into the brain, where accumulation of HS causes the predominantly neurological manifestations of MPS IIIA. The reduction in secondary storage products GM2 and GM3 gangliosides, which are thought to be possible contributors to neuronal damage in lysosomal storage diseases, confirms the biological activity and therapeutic potential of LYS-SAF302.”
About the AAVance clinical trial
The AAVance Phase 2/3 clinical study is designed as an open-label, single-arm, multicenter study of LYS-SAF302 for the treatment of MPS IIIA. The study has been extensively discussed upfront with key opinion leaders, regulators and health technology assessment bodies, as well as with patient representatives. As of today, 19 patients have been treated. The primary objective is to assess the drug efficacy in improving the neurodevelopmental status of patients after 24 months, compared to the expected evolution based on natural history data. Safety, tolerability, effect on behavior, sleep and quality of life will also be collected as secondary endpoints. Lysogene has also set up the sub study, PROVide, collecting supportive video outcomes in the home environment.
Lysogene is a gene therapy Company focused on the treatment of orphan diseases of the central nervous system (CNS). The Company has built a unique capability to enable a safe and effective delivery of gene therapies to the CNS to treat lysosomal diseases and other genetic disorders of the CNS. A phase 2/3 clinical trial in MPS IIIA in partnership with Sarepta Therapeutics, Inc. is ongoing and a phase 1/3 clinical trial in GM1 gangliosidosis is in preparation. In accordance with the agreements signed between Lysogene and Sarepta Therapeutics, Inc., Sarepta Therapeutics, Inc. will hold exclusive commercial rights to LYS-SAF302 in the United States and markets outside Europe; and Lysogene will maintain commercial exclusivity of LYS-SAF302 in Europe. Lysogene is also collaborating with an academic partner to define the strategy of development for the treatment of Fragile X syndrome, a genetic disease related to autism. www.lysogene.com.
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Stéphane Durant des Aulnois
Chief Financial Officer
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