Passage Bio (PASG) Oppenheimer 36th Annual Healthcare Life Sciences Conference summary

Clinical program updates and strategy

• Lead program PBFT02 targets frontotemporal dementia (FTD) with granulin mutation, using a differentiated AAV1 gene therapy delivered via intra-cisterna magna injection, showing robust and durable increases in CSF progranulin levels, with ongoing Phase I/II trials in both FTD-GRN and FTD-C9 cohorts.

• Nine FTD-GRN patients treated across two dose levels; Cohort 3 will enroll 10 patients at the lower dose, focusing on earlier-stage patients (CDR 0.5 and 1) to maximize clinical efficacy.

• Preliminary data show dose-dependent, sustained increases in CSF progranulin, with Dose 1 reaching mid-20s ng/mL and Dose 2 achieving high-normal levels; plasma neurofilament data suggest slowed neurodegeneration compared to natural history.

• Safety profile is generally favorable; SAEs (venous sinus thrombus, LFT increase) occurred only at higher dose and have been addressed with protocol changes, including prophylactic anticoagulation and revised steroid regimen.

• Competitive positioning is strong due to one-time, non-surgical delivery, higher and more durable progranulin levels, and improved patient selection compared to discontinued or less effective competitor programs.

Pipeline and future milestones

• PBFT02 is also being studied in FTD-C9orf72 patients, based on evidence that elevated progranulin may ameliorate TDP-43 pathology, a common pathway in several neurodegenerative diseases.

• Huntington's disease preclinical program targets MSH3 to reduce CAG repeat expansion using AAV-delivered miRNA, with an optimized intraparenchymal delivery approach and clinical candidate nomination expected in the second half of the year.

• Upcoming milestones include interim safety and biomarker data from Dose 2 and extended follow-up from Dose 1 in FTD-GRN, as well as regulatory feedback on registrational trial design.

• Cash runway extends into Q1 2027, with $46 million in cash and an annual burn of $30–35 million.

Insights from competitor programs and trial design

• Learnings from competitor failures (e.g., Alector, AAV9 programs) have informed focus on mechanism, higher target engagement, and earlier patient intervention.

• Future data releases will focus on durability of response, bridging clinical data between doses, and expanded biomarker analysis; CDR data will be shared once sufficient patient numbers and follow-up are achieved.