Passage Bio Reports Positive Interim Data from AAV-Based PBFT02 Gene Therapy Trial for FTD-GRN

PHILADELPHIA, June 23, 2025 – Passage Bio, Inc., a clinical-stage genetic medicines company, today announced updated Phase 1/2 upliFT-D clinical trial data for PBFT02, an AAV-based gene therapy for frontotemporal dementia (FTD) with granulin (GRN) mutations.

Dr. Will Chou, CEO of Passage Bio, highlighted that the one-time AAV gene therapy PBFT02 consistently elevated progranulin (PGRN), the deficient protein in FTD-GRN, and reduced the rate of increase of plasma neurofilament (NfL) levels compared to natural history studies. He noted that the company is refining the AAV therapy’s safety profile and plans to engage regulatory authorities on a future registrational trial design in the first half of 2026.

Key Interim Data for PBFT02:

• CSF Progranulin (PGRN): Dose 1 of AAV-PBFT02 showed robust and durable increases in CSF PGRN expression, with levels rising from below 3 ng/mL at baseline to a mean of 12.4-25.9 ng/mL through 18 months. The first patient on Dose 2 also showed substantial PGRN increase.
• Plasma Neurofilament (NfL): Patients receiving Dose 1 AAV-PBFT02 had a reduced annual rate of plasma NfL increase (4% average) at 12 months, significantly lower than the 28-29% expected in untreated FTD-GRN patients from natural history data.
• Safety: As of June 15, 2025, most treatment-emergent adverse events were mild to moderate. Three of eight patients experienced four serious adverse events, including venous sinus thrombosis and hepatotoxicity (asymptomatic), and one pulmonary embolism (possibly related to AAV treatment). No evidence of dorsal root ganglion (DRG) toxicity or ICM administration complications were observed.

Passage Bio plans to amend the upliFT-D protocol to include low-dose prophylactic anticoagulation and adjust inclusion criteria to focus on prodromal or mild cognitive impairment patients. The company aims to submit the amended protocol in early July 2025 and begin enrollment in Cohort 3 (FTD-GRN) and Cohort 4 (FTD-C9orf72).

Anticipated milestones include:

• Submitting the upliFT-D protocol amendment in July 2025.
• Seeking regulatory feedback on AAV manufacturing comparability in 2H 2025.
• Reporting updated Dose 2 safety and biomarker data in 1H 2026.
• Seeking regulatory feedback on registrational trial design for AAV-PBFT02 in FTD-GRN in 1H 2026.

PBFT02 is an AAV-based gene replacement therapy utilizing an AAV1 viral vector delivered via ICM to introduce a functional GRN gene, aiming to elevate PGRN in the CNS. Preclinical studies demonstrated broad AAV vector distribution and robust PGRN elevations.