Passage Bio Advances AAV Gene Therapy Program for Frontotemporal Dementia and Expands Neurodegenerative Pipeline

March 04, 2026 —

Passage Bio has announced new clinical and corporate updates highlighting continued progress in its gene therapy programs for neurodegenerative diseases, including frontotemporal dementia (FTD) and Huntington’s disease. The Philadelphia-based company reported the latest developments alongside its financial results for the fourth quarter and full year ending December 31, 2025.

A key milestone involves the ongoing Phase 1/2 upliFT-D clinical trial, which is evaluating PBFT02, an investigational AAV1-based gene therapy designed to treat genetic forms of frontotemporal dementia caused by GRN or C9orf72 mutations. The therapy is administered through a single intracisterna magna injection, allowing delivery of the gene therapy directly into the cerebrospinal fluid with the goal of restoring levels of the critical brain protein progranulin (PGRN).

The company recently enrolled the first three patients with FTD-GRN in Cohort 3 of the upliFT-D study. This cohort will evaluate a higher dose of PBFT02 and is expected to enroll a total of ten participants across multiple international clinical sites in the United States, Australia, Brazil, Canada, and Portugal. The trial protocol was recently amended to focus on patients earlier in the course of disease progression and includes a short course of low-dose prophylactic anticoagulation designed to further support patient safety. Passage Bio plans to report updated interim safety and biomarker data from the study and seek regulatory feedback on the potential design of a registrational trial for FTD-GRN in the first half of 2026.

The company has also reached another important milestone in the trial by administering Dose 2 of PBFT02 to the first patient with FTD-C9orf72 in Cohort 4. This cohort is expected to enroll up to five patients. As the first administration of the therapy in this specific patient population, early safety data will be reviewed by the trial’s Independent Data Monitoring Committee (IDMC) before enrollment continues. Additional participants are currently being evaluated for eligibility, and the company expects to proceed with further dosing once the committee completes its review.

Beyond its FTD program, Passage Bio is advancing a preclinical gene therapy approach for Huntington’s disease, a progressive neurodegenerative disorder caused by mutations in the huntingtin (HTT) gene. The company’s strategy focuses on suppressing MSH3, a DNA repair protein known to drive the expansion of CAG repeats that contribute to disease progression. Using an AAV vector carrying a microRNA (miRNA) designed to reduce MSH3 expression, the therapy aims to limit somatic instability in the HTT gene and potentially slow neurodegeneration. Passage Bio expects to select a clinical candidate for this program in the second half of 2026.

Frontotemporal dementia remains a devastating condition with significant unmet medical need. Passage Bio’s leadership emphasized that the company is encouraged by the growing enrollment momentum in the upliFT-D trial and remains focused on advancing its gene therapy pipeline. The company also reported that its current financial resources are expected to support operations into the first quarter of 2027, providing runway to reach several key clinical and regulatory milestones over the next year.