Passage Bio (PASG) investor relations material

Program focus and differentiation

• Lead clinical program targets frontotemporal dementia with granulin mutation; preclinical work ongoing in Huntington's disease.

• Approach uses AAV gene therapy to increase progranulin, aiming for higher and more effective intracellular levels than competitors.

• Differentiates from failed competitor by not disrupting normal cellular processes and targeting earlier-stage patients.

• Excludes more severe patients (CDR 2) and includes those with mild impairment (CDR 0.5–1) to maximize clinical response.

• Expanding to FTD-C9 patients based on preclinical evidence and low incremental study cost.

Clinical development and regulatory strategy

• U.S. FTD-GRN patient population estimated at 3,000–6,000, with genetic testing uptake expected to rise if therapy is available.

• Recruitment has not been an issue due to increased patient engagement and multiple ongoing trials.

• Encouraged by recent FDA guidance supporting single-arm studies for rare, fast-progressing diseases with no available treatments.

• Early and proactive discussions with FDA planned to align on experimental design and statistical analysis.

• Phase I-B top-line data and FDA feedback expected in the first half of next year, seen as a key catalyst.

Biomarker and efficacy insights

• Goal is to raise CSF progranulin levels to or above the upper limit of normal (8 ng/mL); early data from dose two is promising.

• Plasma neurofilament light chain (NfL) used as a biomarker for neurodegeneration; observed increases align with normal aging, suggesting slowed disease progression.

• Robust natural history data available from ALLFTD and GENFI studies, supporting trial design and outcome measures.