developmental domains was also observed and documented for patient 2, despite this patient having severe developmental delay at baseline and a prior history of regression.
| ● | Volumetric MRI data showed meaningful growth in brain volume for patient 1, who was 15 months of age at gene transfer: Volumetric MRI showed increases in brain volume at 12 months compared to baseline for patient 1 in multiple brain regions. Patient 2, who had severe developmental delay at baseline and was 31 months of age at gene transfer, showed a slight decline in brain volume from baseline at six months. |
| ● | Longer-term biomarker data for Beta-galactosidase enzyme activity in CSF and serum showed functional transgene expression: CSF beta-galactosidase activity for both patients increased above levels measured in natural history study (NHS) samples following dosing and were sustained at the upper limit of NHS values. Serum beta-galactosidase activity also increased following administration of PBGM01 for both patients, with patient 1 levels above NHS values at 12-months post-treatment and patient 2 levels normalizing to NHS values at 6-months post-treatment. |
The Imagine-1 study continues to advance. The first patient in Cohort 2, high dose, late infantile, and both patients in Cohort 3, low dose, early infantile, have been dosed. Interim safety and biomarker data from both cohorts are expected in the second half of 2022.
About Imagine-1
Imagine-1 is a Phase 1/2, global, open-label, dose-escalation study of PBGM01 administered by a single injection into the cisterna magna in pediatric subjects with early and late infantile GM1. The primary goal of the study is to first assess safety and tolerability and then efficacy of PBGM01 in patients. The U.S. Food and Drug Administration (FDA) has granted PBGM01 Fast Track, Orphan Drug, and Rare Pediatric Disease designations. PBGM01 has also received an Orphan designation from the European Commission.
To learn more about the clinical trial program, please visit ClinicalTrials.gov: NCT04713475.
About PBGM01
PBGM01 is an AAV-delivery gene therapy currently being developed for the treatment of infantile GM1, in which patients have mutations in the GLB1 gene causing little or no residual beta-galactosidase enzyme activity and subsequent neurodegeneration. PBGM01 utilizes a next-generation AAVhu68 capsid administered through the cisterna magna to deliver a functional GLB1 gene encoding beta-galactosidase to the brain and peripheral tissues. By increasing beta-galactosidase activity, PBGM01 has the potential to reduce accumulation of toxic GM1 gangliosides and reverse neuronal toxicity, thereby restoring developmental potential. In preclinical models, PBGM01 has demonstrated broad brain distribution and high levels of expression of the beta-galactosidase enzyme in both the CNS and critical peripheral organs, suggesting potential treatment for both the CNS and peripheral manifestations of GM1.
About GM1
GM1, a rare monogenic lysosomal storage disease, is caused by mutations in the GLB1 gene, which encodes the lysosomal enzyme beta-galactosidase (β-gal). Reduced β-gal activity results in the accumulation of toxic levels of GM1 gangliosides in neurons throughout the brain, causing rapidly progressive neurodegeneration. GM1 accumulation also results in progressive damage to other tissues including the heart, liver, and bones and manifests with hypotonia (reduced muscle tone), progressive CNS dysfunction, seizures, and rapid developmental regression. Life expectancy for infants with GM1 ranges from 2-10 years, and infantile GM1 represents approximately 60 percent of the global GM1 incidence of 0.5 to 1 in 100,000 live births.
