Core Viewpoint - Passage Bio, Inc. has announced a reverse stock split at a ratio of 1-for-20 to comply with Nasdaq's minimum bid price requirement of $1.00 per share, effective July 14, 2025 [1][2]. Group 1: Reverse Stock Split Details - The reverse stock split will reduce the number of outstanding shares from approximately 62,405,898 to about 3,120,295 [2]. - Proportionate adjustments will be made to the exercise prices and number of shares underlying the Company's equity awards and incentive plans [2]. - The reverse stock split will not change the number of authorized shares or the par value per share [2]. Group 2: Stockholder Information - Registered stockholders holding shares in book-entry form will not need to take action to receive post-split shares [3]. - Stockholders with shares in brokerage accounts will have their positions automatically adjusted, with no action required on their part [3]. - No fractional shares will be issued; stockholders entitled to fractional shares will receive the nearest whole share [3]. Group 3: Company Overview - Passage Bio is a clinical-stage genetic medicines company focused on developing therapies for neurodegenerative diseases [4]. - The lead product candidate, PBFT02, aims to treat conditions like frontotemporal dementia by elevating progranulin levels [4].

PBFT02 Development and Preclinical Results - PBFT02 is an AAV gene therapy designed to deliver functional PGRN to the brain for the treatment of FTD-GRN [13] - In Grn-/- mice, AAV.hGRN vector ICV administration improved lysosomal function, reduced lipofuscin fluorescence in the thalamus, and reduced brain hexosaminidase activity [21, 23] - AAV1 was selected as the vector serotype due to superior hPGRN levels in CSF compared to AAV5 and AAVhu68 in NHPs [28, 29] - In Grn-/- mice, PBFT02 reduced lipofuscin deposition and neuroinflammation in the brain after intra-CSF delivery [34, 37] - ICM administration of PBFT02 enables PGRN delivery throughout the CNS [40] - In NHPs, PBFT02 dose-dependently increased PGRN in CSF up to day 14 [46, 48] - In NHPs, PBFT02 at Dose 1 resulted in approximately 10e4 GC/ug DNA throughout the brain [43] Clinical Trial (upliFT-D) and Safety - The upliFT-D trial is a global Phase 1/2 multi-center, open-label, dose-escalation study with PBFT02 [52, 55] - FTD-GRN Cohort 1 (n = 5) dosing is complete [56] - All four Cohort 1 participants who received a revised immunosuppression regimen had no SAEs or significant immune responses [57] - Cohort 1 interim data shows PBFT02 administration leads to robust and sustained increases in CSF PGRN [58]

Core Insights - Passage Bio, Inc. reported updated data from the Phase 1/2 upliFT-D clinical trial for PBFT02, showing robust and durable increases in cerebrospinal fluid (CSF) progranulin (PGRN) levels and improvements in plasma neurofilament (NfL) levels, indicating potential efficacy in treating frontotemporal dementia (FTD) with granulin mutations [1][2][10] Clinical Trial Data - Dose 1 of PBFT02 increased CSF PGRN levels from below 3 ng/mL at baseline to a mean of 12.4 ng/mL at one month, 19.4 ng/mL at six months, 25.9 ng/mL at 12 months, and 23.8 ng/mL at 18 months [5] - The first patient treated with Dose 2 (50% of Dose 1) saw CSF PGRN levels rise from 1.5 ng/mL at baseline to 7.6 ng/mL at one month, nearing the upper limit of a healthy adult reference range [5] - Plasma NfL levels increased by an average of 4% at 12 months post-treatment, compared to an expected increase of 28% to 29% per year in untreated symptomatic FTD-GRN patients [5] Safety Profile - Treatment emergent adverse events were mostly mild to moderate, with three serious adverse events reported among eight patients, including venous sinus thrombosis and pulmonary embolism [5][6] - No evidence of dorsal root ganglion toxicity was observed, and no complications occurred during the administration of PBFT02 [5] Study Protocol Amendments - The company plans to amend the upliFT-D protocol to include a prophylactic course of low-dose anticoagulation and modify inclusion criteria to allow earlier-stage patients [6][7] - The amended protocol is expected to be submitted to health authorities in early July 2025, with plans to begin enrollment in additional cohorts thereafter [7] Anticipated Milestones - The company aims to seek regulatory feedback on the pivotal trial design for FTD-GRN in the first half of 2026 and report updated interim safety and biomarker data from Dose 2 in the same timeframe [14]

Core Insights - Passage Bio, Inc. reported strong performance in 2024, advancing its PBFT02 program with promising data in FTD-GRN patients, showing robust and durable progranulin expression and early evidence of improvement in a disease progression biomarker [3][6] - The company has extended its cash runway into Q1 2027 by implementing cost-reduction measures and moving to an outsourced analytical testing model [6][15] - Upcoming milestones include reporting 12-month data from Dose 1 and interim safety and biomarker data from Dose 2 in 2H 2025, and seeking regulatory feedback on the registrational trial design in 1H 2026 [6][5] Clinical Trial Updates - Interim data from the upliFT-D clinical trial demonstrated that Dose 1 PBFT02 increased cerebrospinal fluid (CSF) progranulin (PGRN) levels significantly, from below 3 ng/mL at baseline to 13-27 ng/mL at six months and 22-34 ng/mL at 12 months [6] - Plasma neurofilament light chain (NfL) levels were found to be 13% lower than baseline on average at 12 months post-treatment, contrasting with an expected increase of 29% per year based on natural history data [6] - The first FTD-GRN patient has been enrolled to receive Dose 2 PBFT02, which is 50% lower than Dose 1, to facilitate discussions with health authorities regarding a registrational study design [6][3] Financial Performance - As of December 31, 2024, the company reported cash, cash equivalents, and marketable securities totaling $76.8 million, down from $114.3 million as of December 31, 2023 [15] - Research and Development (R&D) expenses for Q4 2024 were $9.6 million, and for the full year, they totaled $40.2 million, compared to $12.1 million and $61.4 million for the same periods in 2023 [15] - The net loss for Q4 2024 was $12.7 million, or $0.20 per share, and for the full year, it was $64.8 million, or $1.07 per share, showing a decrease in losses compared to the previous year [15][21]