Sio Gene Therapies Inc. presented positive interim data from the Company?s ongoing Phase 1/2 study of AXO-AAV-GM1, its adeno-associated viral vector (AAV)9-based gene therapy candidate for the treatment of GM1 gangliosidosis, in an oral presentation at the European Society of Gene & Cell Therapy (ESGCT) Virtual Congress 2021, held from October 19-22, 2021. These follow-up data from five Type II (late-infantile to juvenile) patients in the low-dose cohort and the initial two Type II patients in the high-dose cohort demonstrate an encouraging safety profile and a consistent dose-response in disease biomarkers across the evaluation period. Key findings: Generally well-tolerated at both low and high doses with the majority of adverse events considered mild to moderate To date, there have been no reported serious adverse events attributed to gene therapy in any patients To date, there have been no adverse events leading to study withdrawal in any patients No liver-related adverse events required clinical intervention or had associated clinical sequelae No clinically relevant changes were observed in complement factors, platelet count or other liver function tests Data demonstrate a dose-dependent improvement in key biomarkers of disease activity: ?-galactosidase enzyme activity in the serum and GM1 ganglioside activity in the CSF Serum ?-galactosidase activity achieved a normal range, increasing by 12x and 17x pre-treatment levels, respectively, in both patients in the high-dose cohort at six months All five patients in the low-dose cohort saw a 1.3-2.3x increase in the same timeframe Levels of CSF GM1 ganglioside, the toxic substrate which accumulates in patients with GM1 gangliosidosis and which is associated with disease activity, were normalized in both patients in the high-dose cohort with 42% and 72% reductions, respectively, at six months In the low-dose cohort, a 18-49% decrease was seen in four out of five patients, and a 19% increase in a single patient was seen in the same timeframe GM1 ganglioside levels were below baseline in all five low-dose patients at 12 months MRI assessment of total brain volume and ventricular volume, which decrease and increase respectively in the natural history of the disease, showed the following in the low-dose cohort at 12 months: Total brain volume (excluding ventricles) was maintained within ? 5% in all five patients Ventricular volume remained within ? 15% in four patients and increased by 104% in one patient There was no clinical evidence of overt disease progression in four of five low-dose patients at 12 months and both high-dose patients at six months as assessed by measures of development including the Vineland-3 Adaptive Behavior and Upright and Floor Mobility scales Upcoming Milestones: 1H 2022: Expect to provide data update from Stage 1 of the study, including both Type I (early-infantile) and Type II patients, at future scientific conferences 1H 2022: Expect to engage with the FDA to review Stage 1 data and discuss next steps for clinical development Phase 1/2 Clinical Trial in GM1 Gangliosidosis: The Phase 1/2 study (NCT03952637) is designed to evaluate the safety, tolerability, and potential efficacy of AXO-AAV-GM1 delivered intravenously in children with Type I and Type II GM1 gangliosidosis. Stage 1 is a dose-escalation study in which the low-dose cohort is evaluating a dose of 1.5x1013 vg/kg and the high-dose cohort is evaluating a dose of 4.5x1013 vg/kg in both disease sub-types. Ten patients have been dosed to date in Stage 1 of the clinical study (including eight Type II patients and two Type I patients) Longer-term evaluation of eight Type II patients in the low- and high-dose cohort is ongoing Two Type I patients have received the low dose of AXO-AAV-GM1, and screening for enrollment of Type I patients in the high dose (4.5x1013 vg/kg) cohort is ongoing GM1 gangliosidosis is a progressive and fatal pediatric lysosomal storage disorder caused by mutations in the GLB1 gene that cause impaired production of the ?-galactosidase enzyme. Currently, there are no FDA-approved treatment options for GM1 gangliosidosis.