Passage BIO(PASG) - 2025 Q4 - Annual Results

Financial Position - Cash runway expected to extend into Q1 2027 based on cash, cash equivalents, and marketable securities as of December 31, 2025[3] - As of December 31, 2025, the company reported a cash balance of approximately $46 million, providing a runway into the first quarter of 2027[31] Clinical Development - PBFT02 shows promising data from initial clinical study in FTD-GRN, with a one-time gene replacement therapy approach[4] - The ongoing upliFT-D trial is a global Phase 1/2 study currently enrolling patients, focusing on safety and biomarkers[13] - PBFT02's differentiated gene therapy approach is expected to address the urgent patient need in FTD-GRN with no approved disease-modifying therapies[4] - PBFT02 aims to provide a one-time therapy capable of achieving the highest progranulin levels, addressing underlying pathologies in frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS)[20] - The company plans to initiate discussions with the FDA regarding a registrational study design for FTD-GRN in the first half of 2026[30] - The company expects to declare a clinical candidate for Huntington's disease in the second half of 2026[27] Efficacy and Safety - PBFT02 administration in preclinical studies resulted in CSF hPGRN levels 5x higher than AAVhu68, indicating superior response[10] - PBFT02 demonstrated robust, durable increases in CSF PGRN levels, with a patient increasing from 1.5 ng/mL at baseline to 7.6 ng/mL at month 1[16] - Plasma NfL in PBFT02-treated patients showed a reduced annual rate of change of 3.7% compared to published natural history data of ~29%[17] - PBFT02 demonstrated a generally well-tolerated safety profile with no serious adverse events (SAEs) related to Dose 2, while two SAEs occurred at Dose 1[18] - The mean cerebrospinal fluid (CSF) PGRN level at 12 months was 26 ng/mL, with a durable elevation observed at 18 months in some patients[19] Manufacturing and Production - The company has completed a high-productivity manufacturing process, with a single production lot estimated to yield over 1,000 doses with over 70% full capsids[29] - The company has aligned with the FDA on an analytical approach to establish comparability of the suspension-based manufacturing process for PBFT02[29] Market Context - Estimated prevalence of neurodegenerative diseases includes ~70K for FTD-GRN, ~21K for FTD-C9orf72, and ~18K for Huntington's disease in the US and EU[5] - Key baseline demographics for FTD-GRN participants indicate a mean age of 64.4 years and a mean PGRN level of 36.6 ng/mL in CSF[15] - PBFT02 is positioned as a potentially transformative therapy for FTD-GRN patients, with no approved disease-modifying therapies currently available[32] - The company is pursuing a differentiated gene therapy approach in Huntington's disease, focusing on reducing MSH3 expression to decrease somatic instability in the HTT gene[27]