Passage Bio, Inc. announced updated clinical data from Imagine-1, a Phase 1/2 study of PBGM01, a gene therapy for GM1 gangliosidosis (GM1), are being presented on February 24, 2023 at the 19th Annual WORLDSymposium™. Imagine-1 is a global, open-label, dose-escalation study of the AAVhu68 gene therapy PBGM01 delivered by intra-cisterna magna (ICM) injection in four cohorts of pediatric subjects with early and late infantile GM1 Gangliosidosis (GM1). GM1 is a rare, fatal lysosomal storage disease in which mutations in the GLB1 gene result in very low activity of the enzyme beta-galactosidase (ß-Gal).

The presentations at the WORLDSymposium™ include safety, biomarker and efficacy data from six treated patients in the first three cohorts of the study. The data presented at the 19th Annual WORLDSymposium™ build upon the positive interim safety and biomarker data announced by the company in December 2022, which showed that PBGM01 administration was well tolerated and had a favorable safety profile, with no treatment-related serious adverse events, no complications related to ICM delivery and no evidence of dorsal root ganglion (DRG) toxicity. Moreover, PGBM01 administration resulted in dose dependent increases in CSF ß-Gal activity, as well as dose-dependent decreases in CSF GM1 ganglioside levels.

Updated interim results from cohorts 1-3 of the Imagine-1 study: Magnetic Resonance Imaging (MRI) Severity Score: The MRI severity score, a novel scoring metric, can be used to assess treatment effects on brain volume and white matter integrity for GM1 patients based on baseline and follow-up brain MRI scans. This score measures cerebral and cerebellar atrophy, abnormalities in white matter, and signal abnormalities in the basal ganglia and hippocampi to determine levels of structural damage; Natural history data from late infantile GM1 patients showed MRI severity scores increased in the majority of children over a follow-up period of six months to four years; Preliminary data over a follow-up period of six to 12 months showed PBGM01 administration was associated with stabilization of MRI severity scores in all treated patients. Biomarker Data: PBGM01 administration resulted in decreases in ß-Gal substrate Dp5 levels in urine, suggesting ICM delivery of PBGM01 results in peripheral ß-Gal activity: Both patients who received the high dose (Cohort 2, late infantile) exhibited prominent decreases in urine Dp5 levels; Patients with high baseline levels treated with the low dose of PBGM01 exhibited decreases in urine Dp5 levels.