Passage Bio (PASG) FY Conference Transcript

Summary of Passage Bio (PASG) FY Conference Call - September 05, 2025 Company Overview - Passage Bio is a clinical stage genetic medicines company focused on neurodegenerative diseases, particularly frontotemporal dementia (FTD) [2][3] Core Program: PBFT02 - PBFT02 is the lead clinical program targeting frontotemporal dementia with the GRN mutation, addressing a significant unmet need as there are no approved disease-modifying therapies for this condition [2][4] - The target population includes approximately 18,000 patients with GRN mutation FTD and 21,000 with C9orf72 mutation FTD across the U.S. and Europe [3] Clinical Development and Milestones - The ongoing phase 1/2 study of PBFT02 is a multicenter international open-label dose exploration study, currently active in the U.S., Canada, Portugal, and Brazil [7] - Key upcoming milestones include seeking regulatory feedback on manufacturing comparability in Q4 2025 and reporting dose two data in the first half of 2026 [3][21] Mechanism of Action - PBFT02 utilizes AAV gene therapy to increase levels of progranulin, a protein crucial for CNS cell homeostasis, which is deficient in patients with GRN mutation FTD [4][5] - The administration route is intracisterna magna, allowing for broad CNS biodistribution and lower doses compared to systemic delivery [9][10] Clinical Data and Safety Profile - Initial cohorts have shown promising results, with dose one achieving an average of over 25 nanograms per ml of progranulin levels at 12 months, indicating robust and durable responses [15][18] - The safety profile includes three serious adverse events (SAEs) among eight treated patients, with a decision to implement prophylactic anticoagulation for future patients due to observed venous thromboembolic events [12][20] Biomarker Analysis - Plasma neurofilament levels, a marker of neurodegeneration, showed a significant reduction in treated patients compared to the expected annual increase of 29% in untreated patients, suggesting a potential slowing of disease progression [17][20] - The study is also tracking CSF progranulin levels and clinical dementia rating scales to assess treatment efficacy [9][11] Competitive Landscape - PBFT02 is positioned as a potentially best-in-class therapy, with higher and more durable progranulin levels compared to other therapies in development for FTD [18][19] - Market research indicates a preference for a one-time therapy over monthly treatments, particularly for patients with behavioral dementia [19] Future Directions - Plans to expand the clinical study to include FTD C9 patients, as raising progranulin may also benefit TDP-43 pathology seen in multiple neurodegenerative diseases [20][21] - The company has a cash balance of $58 million, providing a runway into Q1 2027 to continue patient treatment and data collection [22] Conclusion - Passage Bio is advancing its clinical program for PBFT02 with promising early data and a clear regulatory pathway, aiming to address significant unmet needs in neurodegenerative diseases [22]