Lysogene provided an update on clinical results and timelines of the ongoing AAVance phase 2/3 clinical trial with the investigational gene therapy LYS-SAF302 for the treatment of MPS IIIA (NCT03612869). AAVance is an open-label single-arm multicenter trial aimed at evaluating the effectiveness of a one-time intracerebral delivery of a recombinant adeno-associated virus vector rh.10 carrying the N-sulfoglucosamine sulfohydrolase (SGSH) gene (LYS-SAF302, olenasufligene relduparvovec) in children with MPS IIIA. MPS IIIA is caused by mutations in the SGSH gene, which produces an enzyme involved in the catabolism of heparan sulfate.

LYS-SAF302 is intended to deliver a functional copy of the SGSH gene and allow the brain to secrete the missing enzyme. The Company reported positive biomarker data at the WORLDSymposium™ on 10 February 2022, demonstrating biological activity of LYS-SAF302 with reductions, relative to baseline levels, in cerebrospinal fluid concentrations of the storage products heparan sulfate and GM2 & GM3 ganglioside from 6 months post-treatment onwards, as well as serum concentrations of the axonal damage biomarker neurofilament light from 18 months post-treatment onwards. Recruitment and treatment of patients into the main cohort of the study was completed in First Quarter 2020 and AAVance timelines were therefore not impacted by the clinical hold issued by the U.S. Food and Drug Administration (FDA) on the IND in June 2020.

The company expects to report topline data for the main cohort in Third Quarter 2022, along with results of the observational study in children treated with LYS-SAF302, using video and parent interviewing (also called the Patient Reported Outcome Videos [PROVide] study). In terms of safety, white matter abnormalities were observed near injection sites of patients treated in AAVance. From 12 months post-treatment onwards, the abnormalities have stabilized or diminished in size in all patients, based on the conclusions of MRI central readers, and no clinically significant symptoms have been observed that can be directly attributed to white matter abnormalities, according to Company assessment.

Considering these encouraging elements and upon upcoming program readouts, the Company will discuss the path forward with regulators in Fourth Quarter 2022 in the light of the totality of evidence and overall benefit-risk profile of LYS-SAF302.