Passage Bio (PASG) Corporate presentation summary

Strategic focus and pipeline

• Advancing a clinical-stage, one-time gene therapy (PBFT02) for FTD-GRN, with preclinical development in Huntington's disease and potential expansion into ALS and Alzheimer's disease.

• PBFT02 targets genetic forms of FTD caused by GRN mutations, addressing a significant unmet need with no approved disease-modifying therapies.

• Huntington's disease program aims to reduce somatic instability in the HTT gene by decreasing MSH3 expression using AAV-delivered miRNA.

• Cash runway is projected through Q1 2027, supporting ongoing and planned studies.

Clinical and preclinical data highlights

• PBFT02 demonstrated robust, durable increases in CSF progranulin levels at both tested doses, with sustained elevation through 18 months.

• Early biomarker signals indicate PBFT02 slowed brain atrophy and stabilized plasma NFL, suggesting a potential disease-modifying effect in FTD-GRN.

• Preclinical studies showed PBFT02 improved lysosomal function, reduced neuroinflammation, and ameliorated TDP-43 pathology in relevant models.

• AAV1 capsid selected for PBFT02 due to superior CSF PGRN expression and broad CNS biodistribution in NHP studies.

Clinical trial design and safety

• upliFT-D Phase 1/2 trial is enrolling multiple cohorts, using a non-surgical, CT-guided intra-cisterna magna (ICM) administration for broad CNS delivery.

• Primary endpoints include safety, tolerability, and biomarker changes; secondary endpoints assess clinical and imaging outcomes.

• Interim safety profile shows PBFT02 is generally well tolerated, with asymptomatic SAEs limited to Dose 1 and no evidence of DRG toxicity or procedure complications.

• Immune responses to AAV1 were observed but not associated with clinical findings.