Passage Bio Reports Updated Interim Data from upliFT-D Study and Provides Program Update

Core Insights - Passage Bio, Inc. reported updated data from the Phase 1/2 upliFT-D clinical trial for PBFT02, showing robust and durable increases in cerebrospinal fluid (CSF) progranulin (PGRN) levels and improvements in plasma neurofilament (NfL) levels, indicating potential efficacy in treating frontotemporal dementia (FTD) with granulin mutations [1][2][10] Clinical Trial Data - Dose 1 of PBFT02 increased CSF PGRN levels from below 3 ng/mL at baseline to a mean of 12.4 ng/mL at one month, 19.4 ng/mL at six months, 25.9 ng/mL at 12 months, and 23.8 ng/mL at 18 months [5] - The first patient treated with Dose 2 (50% of Dose 1) saw CSF PGRN levels rise from 1.5 ng/mL at baseline to 7.6 ng/mL at one month, nearing the upper limit of a healthy adult reference range [5] - Plasma NfL levels increased by an average of 4% at 12 months post-treatment, compared to an expected increase of 28% to 29% per year in untreated symptomatic FTD-GRN patients [5] Safety Profile - Treatment emergent adverse events were mostly mild to moderate, with three serious adverse events reported among eight patients, including venous sinus thrombosis and pulmonary embolism [5][6] - No evidence of dorsal root ganglion toxicity was observed, and no complications occurred during the administration of PBFT02 [5] Study Protocol Amendments - The company plans to amend the upliFT-D protocol to include a prophylactic course of low-dose anticoagulation and modify inclusion criteria to allow earlier-stage patients [6][7] - The amended protocol is expected to be submitted to health authorities in early July 2025, with plans to begin enrollment in additional cohorts thereafter [7] Anticipated Milestones - The company aims to seek regulatory feedback on the pivotal trial design for FTD-GRN in the first half of 2026 and report updated interim safety and biomarker data from Dose 2 in the same timeframe [14]