Passage Bio (PASG) TD Cowen 45th Annual Healthcare Conference summary

Lead asset and clinical focus

• PBFT02 targets frontotemporal dementia (FTD) patients with granulin mutations, addressing a population of about 18,000 in the US and Europe, with expansion to FTD C9 and ALS underway.

• PBFT02 is an AAV1 gene therapy delivered via a single intra-cisterna magna (ICM) injection, showing durable, elevated CSF progranulin levels well above normal for up to 18 months.

• The therapy leverages cross-correction, benefiting at-risk cells by increasing extracellular progranulin, and demonstrates superior brain distribution and ependymal cell tropism compared to other vectors.

• Seven patients have been dosed in the ongoing phase 1-2 study, with a protocol shift to a lower dose after observing venous sinus thrombus events, supported by robust target engagement at the higher dose.

• Key endpoints include safety, tolerability, CSF progranulin, and neurofilament levels, with early biomarker data suggesting a potential effect on neurodegeneration.

Safety, efficacy, and differentiation

• Most patients experienced no serious adverse events (SAEs); protocol adjustments to steroid regimens improved safety outcomes.

• PBFT02 achieved CSF progranulin levels of 13–27 ng/mL at six months, exceeding both normal and competitor therapy ranges, with durability out to 18 months.

• Plasma neurofilament data in treated patients show a reversal of the typical annual increase seen in untreated FTD GRN, indicating a possible disease-modifying effect.

• PBFT02’s one-time administration offers a practical advantage for patients and families compared to monthly therapies.

• Manufacturing advances include a high-productivity suspension process, enabling over 1,000 doses per 200L batch, and alignment with FDA on potency assays.

Pipeline, regulatory, and financial outlook

• Expansion of PBFT02 to FTD C9 and ALS is ongoing, with preclinical work in Alzheimer’s and Huntington’s disease.

• Additional 12-month data for dose 1 and interim data for dose 2 are expected in the second half of the year; regulatory feedback on registration is planned for H1 2026.

• The company holds $77 million in cash, extending its runway into Q1 2027.

• A business model transition in January included closing the internal analytical lab and moving to an outsourced model to extend the cash runway.

• All GMP manufacturing is outsourced, with no in-house GMP production.