Business Context and Reporting Period
Company: Passage BIO, Inc. (PASG)
Filing Type: Form 8-K (Current Report)
Date: June 23, 2025
Subject: Item 8.01 Other Events – PBFT02 Program Updates for the treatment of frontotemporal dementia with mutations in the GRN gene (FTD-GRN).
Key Financial Metrics
This filing is a clinical update and does not contain financial statements. The text does not provide specific values for revenue, profit, cash flow, margins, debt, or liquidity.
Material Changes and Clinical Data
Biomarker Results (PBFT02)
- Progranulin (PGRN) Levels: Dose 1 treatment resulted in a robust increase in CSF PGRN. Mean levels rose from below 3 ng/mL at baseline to 12.4 ng/mL (1 month), 19.4 ng/mL (6 months), 25.9 ng/mL (12 months), and 23.8 ng/mL (18 months).
- Dose 2 Data: The first patient treated with Dose 2 (50% of Dose 1) saw CSF PGRN increase from 1.5 ng/mL to 7.6 ng/mL at one month, approaching the upper limit of a healthy adult reference range.
- Neurofilament (NfL) Levels: Patients on Dose 1 showed a reduced annual rate of change in plasma NfL (4% increase at 12 months) compared to natural history data expectations (28-29% increase per year).
Safety Profile (as of June 15, 2025)
- Adverse Events: In 5 of 8 patients, all treatment-emergent adverse events were mild to moderate.
- Serious Adverse Events (SAEs): Observed in 3 of 8 patients (4 total SAEs).
- Patients 1 and 7 experienced asymptomatic venous sinus thrombosis (n=2) and hepatotoxicity.
- Patient 8 (Dose 2) experienced a pulmonary embolism in the setting of a concurrent systemic infection; assessed as possibly related to treatment.
- Other Safety: No evidence of dorsal root ganglion toxicity or complications during administration.
Outlook, Management Commentary, and Risks
Program Next Steps
- Protocol Amendment: The Company plans to amend the upliFT-D protocol to include a short course of low-dose prophylactic anticoagulation, supported by the Independent Data Monitoring Committee (IDMC).
- Enrollment: Patient 9 will proceed with additional safety monitoring. Cohort 3 (FTD-GRN) is expected to consist of 5 to 10 patients. Enrollment in Cohort 3 and Cohort 4 (FTD-C9orf72) will begin upon protocol acceptance.
Anticipated Milestones
- July 2025: Submit upliFT-D protocol amendment to health authorities.
- H2 2025: Seek regulatory feedback on suspension-based manufacturing process comparability.
- H1 2026: Report updated interim safety and biomarker data from Dose 2.
- H1 2026: Seek regulatory feedback on registrational trial design in FTD-GRN.
Risks and Contingencies
The filing includes standard forward-looking statement disclaimers regarding the ability to obtain regulatory approval, timing of clinical trials, potential adverse safety events, and dependence on third-party collaborators. Specific risks cited include the possibility that positive early-stage results may not replicate in later trials and potential delays in regulatory feedback.
Investor Verification Checklist
- Verify the timeline for the submission and acceptance of the upliFT-D protocol amendment regarding prophylactic anticoagulation.
- Monitor the safety profile of Patient 9 and subsequent Cohort 3 patients for recurrence of thrombotic events.
- Confirm the Company's cash runway and capital requirements, as this filing does not disclose current liquidity levels.
- Track the regulatory feedback on manufacturing process comparability expected in the second half of 2025.
- Review the natural history data comparisons (ALLFTD) cited for NfL levels to validate the claimed reduction in disease progression markers.