Passage Bio, Inc. announced new interim safety, biomarker, and survival data from cohorts 1-4 in the Imagine-1 clinical study. Imagine-1 is a Phase 1/2, global, open-label, dose-escalation study of the AAVhu68 gene therapy PBGM01 delivered by intra-cisterna magna (ICM) injection in six 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).

Topline interim results from cohorts 1-4 of the Imagine-1 study: Safety (patient follow-up ranged from 8 to 28 months): No treatment-related serious adverse events (SAEs); All treatment-related adverse events (AEs) were mild to moderate in severity; No clinically significant changes in liver function requiring intervention; No evidence of dorsal root ganglion (DRG) toxicity in nerve conduction studies; No complications related to ICM administration; and Favorable immunological profile with no clinically significant immune response. Survival: Imagine-1 study patients showed initial evidence of improved survival relative to natural history data: Natural history data from a meta-analysis of 154 GM1 infants with symptom onset <12 months of age indicates mean survival for infantile GM1 of 18.9 months and no survival beyond 35 months, Infantile GM1 patients receiving PBGM01 showed a survival benefit, with 100% survival beyond 20 months of age (n=3). Biomarkers: Dose 2 of PBGM01 resulted in robust and durable increases in CSF ß-Gal activity: In 3 of 4 children, Dose 2 of PBGM01 resulted in a 4.7-16.1x increase in CSF ß-Gal activity at 30 days post-treatment relative to baseline, exceeding average levels seen in healthy adults and GM1 Natural History Study (NHS), Increased CSF ß-Gal activity was able to be sustained for up to 12 months; Dose 2 of PBGM01 decreased CSF GM1 ganglioside levels and demonstrated the ability to achieve normal adult levels at one-year post-dose, GM1 ganglioside levels continued to decline over time in all patients treated with Dose 2; Effects on CSF ß-Gal activity and GM1 gangliosides were dose-dependent, with Dose 1 of PBGM01 exhibiting modest effects.

The company has treated the first patient at Dose 3 and is actively recruiting additional patients in the Imagine-1 study for Cohort 5 (late infantile) and Cohort 6 (early infantile). The amended study protocol has been approved at several clinical trial sites, including in Brazil, Canada, Turkey and the United States. Dosing of patients in Cohorts 5 and 6 may occur concurrently, and the company expects to report initial safety and biomarker data from Dose 3 by mid-2024.