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I – Gene & Cell Therapy Trials in Progress -> Gene & Cell Therapy Trials in Progress

Interim Safety, Biomarker, and Efficacy Data From Imagine-1: A Phase 1/2 Open-label, Multicenter Study to Assess the Safety, Tolerability, and Efficacy of a Single Dose, ICM Administration of PBGM01 in Subjects with Type I (Early Onset) and Type IIa (Late Onset) Infantile GM1 Gangliosidosis (GM1)

Type: Oral Abstract Session

Presentation Details
Session Title: Late-Breaking Abstracts II
Location: Ballroom C
Start Time: 5/18/2022 8:30
End Time: 5/18/2022 8:45

Introduction: GM1 is a neurodegenerative autosomal recessive disorder resulting from mutations in the human galactosidase beta 1 gene (GLB1), which encodes beta-galactosidase (β-gal). Currently, no disease-modifying treatments exist. Methods: A first-in-human, global interventional, multicenter, single-arm, dose‑escalation, adaptive design clinical trial of PBGM01 (NCT04713475 [ClinicalTrials.gov]; 2020-001109-22 [EudraCTNumber]), an adeno-associated viral vector serotype Hu68 carrying a DNA sequence encoding the human GLB1 gene, is underway. A single ICM (intra-cisterna magna) administration of PBGM01 delivers a functional copy of the GLB1 gene directly to the CSF. Patients (pts) with early onset (EO, Type I, ≥4 to <24 mo of age at enrollment) and late onset (LO, Type IIa, ≥6 to <36 mo of age at enrollment) infantile GM1 have enrolled in a dose escalation phase testing low- (LD) and high dose- (HD) PBGM01. Primary outcomes (OCs) include number of subjects with treatment-related AEs, SAEs, and clinically significant laboratory abnormalities, nerve conduction study changes, and immune response to PBGM01 (CSF & serum). Secondary OCs include longitudinal neurodevelopmental assessments (eg, Vineland-II [V-II] & Bayley-III [B-III]), change in key biomarker (BM) activity (CSF & serum β-gal; CSF GM1 ganglioside), neuroimaging, and QoL assessments. Results: Pts have been enrolled in Cohort 1 (LD, LO), with 2 (HD, LO) and 3 (LD, EO) to follow. Early data have shown PBGM01 was well-tolerated and had a favorable safety profile as no SAEs, complications related to ICM injection, or evidence of DRG toxicity were observed. Initial assessments showed increases in CSF and serum β-gal activity post-treatment in both pts in Cohort 1, above NHS patient values. Improvements were documented (V-II) and directly observed (B-III) in all developmental areas through the completed assessment periods, notable as Pt 2 had a severe developmental delay at baseline. The latest safety, BM, and longitudinal developmental data will be presented; results from vector DNA distribution, immunogenicity studies, and brain volumetric changes as assessed by MRI will also be presented. Conclusion: Interim safety, BM, and developmental data from these initial pts support the effectiveness of PBGM01 as a disease-modifying treatment of infantile GM1.

David A. Weinstein1, Caroline A. Hastings2, Debra-Lynn Day-Salvatore3, Can Ficicioglu4, Chester B. Whitley5, Michal Inbar-Feigenberg6, Geneviève Bernard7,8, Roberto Giugliani9, Julien Baruteau10, Fatih S. Ezgü11, Jeanine R. Jarnes5, Yan G. Ni1, Pruthvi Nagilla1, Victoria L. Ballard1, Thomas F. Haws1, Michael H. Gelb12, Mark S. Forman1

1Passage Bio, Inc., Philadelphia, PA,2UCSF Benioff Children’s Hospital, Oakland, CA,3Saint Peter’s University Hospital, New Brunswick, NJ,4Children's Hospital of Philadelphia, Philadelphia, PA,5University of Minnesota, Minneapolis, MN,6The Hospital for Sick Children (SickKids), Toronto, ON, Canada,7McGill University, Montreal, QC, Canada,8McGill University Health Centre, Montreal, QC, Canada,9Federal University of Rio Grande do Sul, Porto Alegre, Brazil,10Great Ormond Street Hospital for Children, London, United Kingdom,11Gazi University, Gazi, Turkey,12University of Washington, Seattle, WA
  D.A. Weinstein: 1; Commercial Interest i.e. Company X; Passage Bio, Inc.; Philadelphia, PA. 1; What was received? i.e. Honorarium; Stock Options; Stock. 1; For what role? i.e. Speaker; Employee.

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