8-K: Passage Bio Reports Promising Data and Extends Cash Runway into Q1 2027

Passage Bio announced positive interim data from its PBFT02 program in FTD-GRN patients, demonstrating durable progranulin expression and early evidence of improvement in a disease progression biomarker, along with an extended cash runway into the first quarter of 2027.

Summary

• Passage Bio reported its financial results for the fourth quarter and full year 2024, along with recent business highlights.
• Interim data from the upliFT-D clinical trial showed that Dose 1 of PBFT02 consistently increased cerebrospinal fluid (CSF) progranulin (PGRN) levels 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).
• Plasma neurofilament light chain (NfL) levels, a disease progression biomarker, were 13% lower than baseline on average at 12 months (n=2) post-treatment, compared to an expected increase of 29% per year based on natural history data.
• The company enrolled the first FTD-GRN patient to receive Dose 2 PBFT02, which is 50% lower than Dose 1.
• Passage Bio extended its cash runway into 1Q 2027 by moving to an outsourced analytical testing model and reducing operating expenses.
• Cash, cash equivalents, and marketable securities were $76.8 million as of December 31, 2024, compared to $114.3 million as of December 31, 2023.
• R&D expenses were $9.6 million for the quarter ended December 31, 2024, and $40.2 million for the year ended December 31, 2024, compared to $12.1 million and $61.4 million for the same periods in 2023.
• G&A expenses were $4.7 million for the quarter ended December 31, 2024, and $25.0 million for the year ended December 31, 2024, compared to $6.3 million and $41.6 million for the same periods in 2023.
• Net loss was $12.7 million for the quarter ended December 31, 2024, and $64.8 million for the year ended December 31, 2024, compared to $16.8 million and $102.1 million for the same periods in 2023.

Sentiment

Score: 7

Explanation: The document presents a mix of positive clinical data, extended cash runway, and reduced operating expenses, balanced by ongoing losses and a decrease in cash reserves. The overall tone is cautiously optimistic.

Positives

• PBFT02 demonstrated durable, elevated CSF PGRN and early evidence of reduction in plasma NfL levels.
• The company enrolled the first FTD-GRN patient to be treated with Dose 2 PBFT02.
• Passage Bio extended its cash runway into 1Q 2027.
• The company completed the process development and scale-up of a high-productivity, suspension-based manufacturing process for PBFT02.
• R&D and G&A expenses decreased compared to the previous year.

Negatives

• The company reported a net loss of $64.8 million for the year ended December 31, 2024.
• Cash and cash equivalents decreased from $114.3 million to $76.8 million year over year.

Risks

• The company's ability to develop and obtain regulatory approval for its product candidates is subject to risks and uncertainties.
• Clinical trials are subject to risks, including the ability to manage clinical activities, unexpected concerns from data analysis, and regulatory requirements.
• The occurrence of adverse safety events could impact the program.
• The company is dependent on collaborators and other third parties for development and manufacturing.
• Current and potential delays, work stoppages, or supply chain disruptions could impact the company.

Future Outlook

Passage Bio expects its current cash, cash equivalents, and marketable securities to fund operations into 1Q 2027. The company anticipates reporting 12-month data from Dose 1 and interim safety and biomarker data from Dose 2 in 2H 2025 and plans to seek regulatory feedback on registrational trial design in 1H 2026.

Management Comments

• We are pleased to report strong performance in 2024 as we meaningfully advanced our PBFT02 program, delivering promising data in FTD-GRN patients showing robust, durable progranulin expression and early evidence of improvement in a disease progression biomarker, said Will Chou, M.D., president and chief executive officer of Passage Bio.
• Furthermore, we completed the process development and scale-up of a high-productivity, suspension-based manufacturing process for PBFT02 and are well-positioned for late-stage development.
• As we enter 2025, we remain focused on execution of our ongoing upliFT-D trial in FTD-GRN and are excited to expand enrollment to include FTD patients with C9orf72 gene mutations.
• We look forward to building upon the encouraging data generated to date and engaging with health authorities to explore the registrational pathway for this promising, one-time therapy to address a significant unmet patient need.

Industry Context

Passage Bio is focused on developing gene therapies for neurodegenerative diseases, a field with significant unmet need. The company's PBFT02 program targets FTD-GRN, a genetic form of frontotemporal dementia, and is also exploring potential applications in FTD-C9orf72, ALS, and Alzheimer's disease. The development of one-time therapies with durable effects is a key trend in the gene therapy space.

Comparison to Industry Standards

• The company compares its CSF PGRN levels achieved with PBFT02 to those achieved by Alector with an anti-sortilin antibody and Lilly/Prevail with an AAV9 gene therapy.
• Passage Bio claims that PBFT02 is uniquely positioned to offer a one-time therapy capable of achieving the highest progranulin levels.
• The company is leveraging recent GTx precedents for utilizing natural history data as an external control, which is a strategy used to accelerate drug development in rare diseases.

Stakeholder Impact

• Shareholders: The extended cash runway and positive clinical data are likely to be viewed favorably by shareholders.
• Patients: The development of PBFT02 offers hope for patients with FTD-GRN and other neurodegenerative diseases.
• Employees: The reduction in operating expenses may have involved workforce reductions, impacting employees.
• Collaborators: The company's reliance on collaborators highlights the importance of these relationships for the success of the program.

Next Steps

• Evaluate Dose 2 in subsequent Cohort 2 patients.
• Report 12-month Dose 1 and interim Dose 2 data in 2H 2025.
• Seek regulatory feedback on registrational trial design in 1H 2026.
• Initiate dosing of FTD-C9orf72 patients in 1H 2025.
• Advance Huntingtons disease preclinical program.

Key Dates