Passage Bio (PASG) investor relations material

Key program highlights

• Lead program PBFT02 targets frontotemporal dementia (FTD) with GRN and C9orf72 mutations, affecting about 39,000 patients in the US and Europe.

• PBFT02 uses AAV1 capsid for gene therapy, administered via intracisterna magna for broad CNS distribution and lower dosing.

• Phase 1/2 trial is open-label, multicenter, with sites in the US, Canada, Portugal, and Brazil; three dosing cohorts planned.

• Key biomarkers include CSF progranulin and plasma neurofilament levels, with clinical response measured by a modified dementia rating scale.

• Upcoming milestones: regulatory feedback on manufacturing in H2 2025, interim data and registrational trial design in H1 2026.

Clinical data and safety

• Dose one showed robust, durable increases in CSF progranulin, exceeding healthy adult levels at 12 and 18 months.

• Dose two, at half the level, also reached normal progranulin range at 30 days; all future patients to receive this dose.

• Plasma neurofilament levels, a marker of neurodegeneration, increased only 3.7% per year in treated patients vs. 29% in untreated.

• Three of eight patients experienced venous thromboembolic events; protocol now includes prophylactic anticoagulation with low-dose apixaban.

• No clinically significant immune responses or complications from the administration procedure observed.

Competitive positioning and future plans

• PBFT02 achieves higher and more durable progranulin levels than other therapies, including monthly IV antisortillin antibody and another AAV9 gene therapy.

• One-time administration is expected to be preferred by patients and families over chronic therapies.

• Protocol updates will include earlier-stage patients and exclude more severe cases.

• Expansion to FTD C9 patients planned for later this year; preclinical Huntington’s disease program advancing.

• Cash balance of $58 million provides runway into Q1 2027.