Passage Bio (PASG) Canaccord Genuity 44th Annual Growth Conference & Private Company Showcase 2024 summary

Program overview and clinical progress

• Lead gene therapy targets frontotemporal dementia (FTD) with granulin mutation, using a one-time AAV1 vector.

• PBFT02 is being expanded to FTD-C9, ALS, and Alzheimer's populations, with initial focus on patients with granulin deficiency.

• Ongoing phase I/II study uses an open-label, dose-escalation design across multiple international sites.

• Strong initial response in cohort one led to maintaining the same dose for cohort two, accelerating recruitment.

• In-house manufacturing and recent out-licensing of pediatric portfolio provide financial runway through Q2 2026.

Clinical data and safety

• Five patients treated in cohort one; four received higher immunosuppression with no serious adverse events (SAEs).

• No evidence of DRG toxicity or complications from intracisternal magna (ICM) administration.

• ICM delivery enables broad CNS biodistribution at lower doses and reduced immunosuppression compared to IV.

• Safety and target engagement data to be updated at ISFTD meeting, including some 12-month data.

• No known toxicity from high progranulin levels; FDA approved starting at current dose for FTD-C9.

Efficacy and biomarkers

• CSF progranulin levels in treated patients exceeded normal and competitor ranges, showing strong target engagement.

• Consistency of high progranulin levels across patients may increase likelihood of clinical response.

• Preclinical evidence supports high progranulin levels reducing TDP-43 pathology, relevant for FTD and ALS.

• Exploratory biomarkers (lysosomal dysfunction, neurodegeneration) will require more patient data for meaningful analysis.

• Durability of response and consistent biomarker changes are key for advancing to pivotal studies.