Passage Bio (PASG) Leerink Global Healthcare Conference 2025 summary

Program overview and disease background

• Lead program PBFT02 is a one-time AAV1 gene therapy for FTD-GRN, a genetic form of frontotemporal dementia with no approved disease-modifying therapies.

• PBFT02 is administered directly to the CSF and shows durable, elevated CSF progranulin levels in early clinical data.

• The therapy targets an orphan disease with about 18,000 FTD-GRN and 21,000 FTD-C9orf72 patients in the US and Europe.

• Preclinical work is ongoing for Alzheimer's patients with low progranulin and a Huntington's program is in the pipeline.

Clinical data and safety profile

• Phase 1/2 study is multinational, with robust progranulin response at the lowest dose prompting a move to lower dosing.

• Seven patients dosed; two experienced venous sinus thrombosis, prompting increased immunosuppression and dose reduction.

• No complications from administration or DRG toxicity; lower dosing aims to reduce inflammatory response.

• CSF progranulin levels in treated patients are well above normal and durable out to 18 months.

• Early biomarker data show a reduction in plasma neurofilaments, suggesting a potential effect on neurodegeneration.

Competitive landscape and differentiation

• PBFT02 achieves higher and more durable CSF progranulin levels than monthly anti-sortillin antibody or AAV9 therapies.

• One-time administration is positioned as a major advantage for patients with behavioral dementia.

• Manufacturing process scaled to commercial readiness, with a 200-liter batch able to treat about 1,000 patients.