Passage Bio Announces Promising Interim Clinical Data from First Eight Patients with GM1 Gangliosidosis in Imagine-1 Study - Seite 2

“Our momentum in the Imagine-1 study continues to be strong as the program progresses to evaluate its highest dose level, Dose 3, in patients with early and late infantile GM1,” Dr. Chou continued. “We are excited to share that we have treated the first patient at Dose 3, and we are actively recruiting additional patients at clinical trial sites across multiple countries. We look forward to sharing initial data from Dose 3 patients by mid-2024 and want to express our deepest gratitude for the dedication and collaboration demonstrated by the families and investigators who have participated in our Imagine-1 trial.”

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
• 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 monthsⁱ
  • Infantile GM1 patients receiving PBGM01 showed a survival benefit, with one hundred percent survival beyond 20 months of age (n=3)
    

Biomarkers

• Dose 2 of PBGM01 resulted in robust and durable increases in CSF β-Gal activity
  • In 3 of 4 children, Dose 2 of PBGM01 resulted in a 4.7-16.1x increase in CSF β-Gal activity at 30 days post-treatment relative to baseline, exceeding average levels seen in healthy adults and GM1 Natural History Study (NHSⁱⁱ)
  • Increased CSF β-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 β-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.