Passage Bio (PASG) investor relations material

Program overviews and recent milestones

• Companies focus on gene therapies for neurodegenerative diseases, emphasizing local delivery and in-house manufacturing to improve safety and reduce costs.

• Recent milestones include positive phase II data in Parkinson's, Huntington's, and frontotemporal dementia, with several programs approaching BLA filings.

• AI partnerships are being leveraged to analyze clinical data and enhance endpoint robustness, particularly in Parkinson's studies.

• Durable biomarker engagement and stabilization of neurodegeneration markers have been demonstrated in clinical trials.

• Preclinical programs are advancing, targeting novel pathways such as DNA damage response in Huntington's disease.

Key challenges in gene therapy for neurodegenerative diseases

• Delivery to the correct brain regions remains a primary challenge, with local administration favored for precision and safety.

• Slow disease progression complicates clinical trial design and endpoint measurement, making it difficult to demonstrate efficacy.

• Heterogeneity among patients requires advanced statistical and AI methods to distinguish true treatment effects from noise.

• Regulatory agencies are increasingly open to novel endpoints and trial designs, especially for rare diseases with high unmet need.

• Safety concerns persist, but local delivery and lower vector doses have shown improved safety profiles compared to systemic approaches.

Regulatory and access considerations

• FDA is showing flexibility for rare, high-unmet-need diseases, allowing single-arm studies with supportive evidence.

• Use of natural history data and external controls is gaining acceptance to address patient heterogeneity.

• AI-driven analysis is being used to enhance endpoint robustness and reduce bias in imaging and clinical data.

• Access challenges include the need for specialized centers and trained surgeons, but procedures are being designed to fit existing hospital workflows.

• Strong clinical data is expected to drive rapid adoption despite procedural complexities.