Passage Bio disclosed it will cut roughly 75% of staff after the FDA required a different registrational trial design for PBFT02 in frontotemporal dementia with granulin mutations (FTD-GRN). The company said the agency did not support a single-arm trial and instead requested a randomized controlled design, complicating the ethical and financial path forward. Alongside workforce reductions, Passage launched a strategic review and said it is evaluating alternatives that could include a merger or acquisition, asset sales, and licensing. The company’s update also referenced positive interim Phase 1/2 upliFT-D data suggesting PBFT02 may slow neurodegeneration, with changes in brain atrophy and plasma neurofilament biomarkers. The juxtaposition of early signal with major FDA design friction underscores how trial architecture can rapidly reshape biotech viability and capital planning.