Passage Bio Announces Positive Interim Clinical Data from First Six Patients with GM1 Gangliosidosis in Imagine-1 Study

Passage Bio

PHILADELPHIA, PA — Passage Bio, Inc. (Nasdaq: PASG) this week announced new interim safety, biomarker, and clinical development results from cohorts 1-3 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 (β-Gal).

The interim data include six treated patients from the first three cohorts. Cohort 1 (late infantile, low dose), Cohort 2 (late infantile, high dose) and Cohort 3 (early infantile, low dose) each consisted of two patients. Cohort 4 (early infantile, high dose) patients have been dosed and data is expected by mid-2023.

“We are excited to share interim data from this first six patients in our Imagine-1 study, which further reinforce our confidence in PBGM01 as a promising treatment option for GM1 gangliosidosis,” said William Chou, M.D., chief executive officer of Passage Bio. “The goals of this Phase 1/2 study are to establish the safety profile for PBGM01, determine the optimal dose for therapeutic effect, and gain understanding of how PBGM01 can benefit patients across infantile GM1 populations. We are encouraged by emerging trends in the data and look forward to receiving results from Cohort 4 to further inform our program and support interactions with regulatory authorities. We couldn’t be more thankful for the conviction and perseverance of the families and investigators participating in our Imagine-1 trial.”

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Topline interim results from cohorts 1-3 of the Imagine-1 study

Safety (patient follow-up ranged from three to 20 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


  • PBGM01 administration resulted in dose-dependent increases in CSF β-Gal activity, with both patients who received the high dose (Cohort 2, late infantile) exhibiting increases in enzyme activity well above baseline
    • For the first patient in Cohort 2, enzyme activity increased 4.7-fold and 3.6-fold over baseline at 30 days and six months, respectively
    • For the second patient in Cohort 2, enzyme activity increased 5.2-fold over baseline at 30 days
    • Patients treated with the low dose exhibited variable responses in enzyme activity at 30 days, which ranged from 1.2 to 2.8-fold increase over baseline at six months
  • PBGM01 administration also resulted in dose-dependent decreases in CSF GM1 ganglioside levels, with both patients in Cohort 2 showing decreases in substrate levels from baseline
    • For the first patient in Cohort 2, levels decreased by 30% and 75% from baseline at 30 days and six months, respectively
    • For the second patient in Cohort 2, levels decreased by 21% from baseline at 30 days
    • Patients treated with the low dose exhibited variable levels of response

Clinical Development

  • Patients with milder development delay at dosing showed a higher response to PBGM01 treatment, as determined by investigators and caretakers
    • Patients 1 (late infantile, low dose) and 5 (early infantile, low dose), who both demonstrated modest developmental delay at baseline, showed increases in overall developmental age
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“The new interim data from cohorts 1-3 continue to strengthen the favorable safety profile of PBGM01, with no treatment-related serious adverse events, no complications related to ICM administration and no evidence of DRG toxicity,” said Mark Forman, M.D., Ph.D., chief medical officer of Passage Bio. “We are also seeing dose-dependent increases in CSF β-Gal enzyme activity, decreases in CSF GM1 ganglioside levels, and meaningful improvement across developmental areas on both the Vineland and Bayley scales in a subset of patients with more modest developmental delay at baseline. We look forward to presenting additional data from cohorts 1-3 at the 19th Annual WORLDSymposium in February 2023.”

Passage has completed dosing of PBGM01 in the dose-escalation portion of the study and will evaluate dosing further patients at the current high dose and/or a higher dose as data from cohorts 1-4 mature. Data from Cohort 4 is anticipated by mid-2023.

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