Passage Bio Announces Positive Interim Safety and Biomarker Data and Advances Phase 1/2 Trial of PBGM01 in GM1 Gangliosidosis

– Independent Data Monitoring Committee recommends proceeding with two additional planned patient cohorts, which are now being recruited in parallel

– Positive safety profile, including no serious adverse events, no complications related to intra-cisterna magna injection and no evidence of dorsal root ganglion toxicity

– Intra-cisterna magna delivery resulted in substantial increases in beta-galactosidase enzyme activity observed in both cerebrospinal fluid and serum

– Additional data to be shared in late-breaker presentation at the 18th Annual WORLDSymposium, February 11, 2022

– Management to host a conference call and webcast today at 8 a.m. ET

Excerpt from the Press Release:

PHILADELPHIA, Dec. 17, 2021 (GLOBE NEWSWIRE) — Passage Bio, Inc. (Nasdaq: PASG), a clinical-stage genetic medicines company focused on developing transformative therapies for central nervous system (CNS) disorders, today announced that the Independent Data Monitoring Committee (IDMC) recommended proceeding to additional planned cohorts 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 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. The primary goal of the study is to first assess safety and tolerability and then efficacy of PBGM01.

The IDMC recommendation followed positive interim safety and biomarker data from Cohort 1 (n=2) patients with late infantile GM1 who received a low dose of PBGM01. Based on the IDMC recommendation, Passage Bio has initiated recruitment in parallel for both a high-dose cohort (Cohort 2) of patients with late infantile GM1 and a low-dose cohort (Cohort 3) of patients with early infantile GM1.

Passage Bio was also able to compare the Cohort 1 interim results with initial data from an ongoing natural history study being run in collaboration with the Orphan Disease Center at the University of Pennsylvania. This study measured both cerebrospinal fluid (CSF) and serum levels of beta-galactosidase in patients with juvenile and early infantile GM1. The natural history study data showed mean values of enzyme activity in CSF and serum comparable to the baseline levels observed in both patients in Cohort 1 in the Imagine-1 trial.

Topline interim results from the Imagine-1 Cohort 1 (patient 1 data through eight months and patient 2 data through two months):

• Safety
  • No serious adverse events (AEs)
  • Reported AEs were all mild to moderate; all moderate AEs resolved without intervention and were deemed not treatment related
  • No complications related to ICM injection were observed
  • No evidence of dorsal root ganglion (DRG) toxicity in nerve conduction studies
• Beta-galactosidase enzyme activity levels
  
  • Following PBGM01 administration, beta-galactosidase activity in CSF and serum increased in both patients.
    • CSF
      • For patient 1, enzyme activity at 30 days was 1.5-fold over baseline and the increase was maintained at six months
      • For patient 2, enzyme activity at 30 days was 4.8-fold over baseline
    • Serum
      • For patient 1, enzyme activity was slightly above baseline at 30 days, 1.7-fold over baseline at three months and the increase was maintained at six months
      • For patient 2, enzyme activity at 30 days was 1.2-fold over baseline
• GM1 gangliosides in CSF
  • Large differences were observed at baseline, with patient 2 showing baseline values four times higher than patient 1
  • For patient 1, levels increased approximately 85 percent at 30 days and remained stable at that level at six months.
  • For patient 2, levels decreased approximately 46 percent at 30 days consistent with high increases in CSF enzyme activity

“We are extremely encouraged by the interim data in this first low dose cohort of patients with late infantile GM1. The favorable safety profile of PBGM01 as well as the increase in beta-galactosidase activity in both CSF and serum with the lowest dose at this early timepoint supports moving forward in two additional cohorts.” said Bruce Goldsmith, Ph.D., president and chief executive officer, Passage Bio. “We are most grateful to the children with GM1, their families and caregivers, as well as the clinical trial investigators who have chosen to participate in Imagine-1. We also could not have progressed to this point without our strong collaboration with University of Pennsylvania’s Gene Therapy Program, whose experience in developing optimal AAV technologies is unmatched. The results from the first cohort reinforce our confidence in our selected AAV technology as well as the ICM route of administration for our GM1 program and our additional clinical programs.”

Roberto Giugliani, M.D., Ph.D., Department of Genetics UFRGS and Medical Genetics Service HCPA, Porto Alegre, Brazil, who is an expert in lysosomal storage diseases and a principal investigator in the Imagine-1 study, said: “Children with infantile GM1 experience a rapid decline in neurologic function and unfortunately there are no disease-modifying treatments available to them. The disease is devastating to patients and their families, so I am encouraged by the early data with PBGM01 – that it was not only well-tolerated but also showed an increase in activity of the beta-galactosidase enzyme in both serum and CSF. I look forward to the continued clinical advancement of PBGM01 and learning its potential for GM1 patients.”

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