Passage Bio Reported Updated Data From The Ongoing Phase 1/2 upliFT-D Trial Of PBFT02 For Frontotemporal Dementia With Granulin Mutations

Updated interim data from FTD-GRN patients treated with Dose 1 PBFT02:

Biomarkers

• Dose 1 of PBFT02 treatment resulted in a robust and durable increase in PGRN expression.
  • PBFT02 consistently increased CSF PGRN expression in all patients from below 3 ng/mL at baseline to 13 – 27 ng/mL at six months (n=4) and 22 – 34 ng/mL at 12 months (n=2).
  • CSF PGRN levels generally plateaued by month 6 and have remained durable through the longest available follow-up of 18 months (n=1).
• Plasma NfL levels were 13% lower than baseline on average at 12 months (n=2) post-treatment.
  • In contrast, in untreated symptomatic FTD-GRN patients, plasma NfL levels are expected to increase by 29% per year, according to published natural history datai.
• Plasma PGRN expression remained below healthy reference levels across all patients.

Safety (patient follow-up up to 18 months as of December 9, 2024, data cutoff)

• In 5 of 7 patients, all treatment emergent adverse events (AEs) were mild to moderate in severity.
• 2 of 7 patients experienced a total of 3 serious adverse events (SAEs). As previously disclosed, the first treated patient experienced the asymptomatic SAEs of venous sinus thrombosis (VST) and hepatotoxicity, leading to a revised immunosuppression regimen in all subsequent patients (1,000 mg IV methylprednisolone on days 1-3 followed by 60 mg oral prednisone through day 60). Patient 7 also experienced the SAE of VST, which was asymptomatic and completely resolved prior to day 30 following treatment with anticoagulants. This patient had no evidence of hepatotoxicity, immune response or other laboratory abnormalities and remains enrolled in the clinical study.
• No evidence of clinically significant immune responses in any patient who received the revised immunosuppression regimen.
• No evidence of dorsal root ganglion (DRG) toxicity, as measured by nerve conduction studies, and no complications during intra cisterna magna (ICM) administration were observed across any of the seven treated patients.