Summary of Passage Bio (PASG) FY Conference Call - September 05, 2025 Company Overview - Passage Bio is a clinical stage genetic medicines company focused on neurodegenerative diseases, particularly frontotemporal dementia (FTD) [2][3] Core Program: PBFT02 - PBFT02 is the lead clinical program targeting frontotemporal dementia with the GRN mutation, addressing a significant unmet need as there are no approved disease-modifying therapies for this condition [2][4] - The target population includes approximately 18,000 patients with GRN mutation FTD and 21,000 with C9orf72 mutation FTD across the U.S. and Europe [3] Clinical Development and Milestones - The ongoing phase 1/2 study of PBFT02 is a multicenter international open-label dose exploration study, currently active in the U.S., Canada, Portugal, and Brazil [7] - Key upcoming milestones include seeking regulatory feedback on manufacturing comparability in Q4 2025 and reporting dose two data in the first half of 2026 [3][21] Mechanism of Action - PBFT02 utilizes AAV gene therapy to increase levels of progranulin, a protein crucial for CNS cell homeostasis, which is deficient in patients with GRN mutation FTD [4][5] - The administration route is intracisterna magna, allowing for broad CNS biodistribution and lower doses compared to systemic delivery [9][10] Clinical Data and Safety Profile - Initial cohorts have shown promising results, with dose one achieving an average of over 25 nanograms per ml of progranulin levels at 12 months, indicating robust and durable responses [15][18] - The safety profile includes three serious adverse events (SAEs) among eight treated patients, with a decision to implement prophylactic anticoagulation for future patients due to observed venous thromboembolic events [12][20] Biomarker Analysis - Plasma neurofilament levels, a marker of neurodegeneration, showed a significant reduction in treated patients compared to the expected annual increase of 29% in untreated patients, suggesting a potential slowing of disease progression [17][20] - The study is also tracking CSF progranulin levels and clinical dementia rating scales to assess treatment efficacy [9][11] Competitive Landscape - PBFT02 is positioned as a potentially best-in-class therapy, with higher and more durable progranulin levels compared to other therapies in development for FTD [18][19] - Market research indicates a preference for a one-time therapy over monthly treatments, particularly for patients with behavioral dementia [19] Future Directions - Plans to expand the clinical study to include FTD C9 patients, as raising progranulin may also benefit TDP-43 pathology seen in multiple neurodegenerative diseases [20][21] - The company has a cash balance of $58 million, providing a runway into Q1 2027 to continue patient treatment and data collection [22] Conclusion - Passage Bio is advancing its clinical program for PBFT02 with promising early data and a clear regulatory pathway, aiming to address significant unmet needs in neurodegenerative diseases [22]

Company Overview - Passage Bio, Inc. is a clinical stage genetic medicines company focused on improving the lives of patients with neurodegenerative diseases [3] - The company's lead product candidate, PBFT02, aims to treat neurodegenerative conditions such as frontotemporal dementia by elevating progranulin levels to restore lysosomal function and slow disease progression [3] Upcoming Events - Management will participate in the H.C. Wainwright 27th Annual Global Investment Conference from September 8-10, 2025, in New York City [1] - Will Chou, M.D., president and CEO, will present an overview of the company and engage in one-on-one meetings with investors [2] - A video webcast of the presentation will be available to registered attendees starting September 5, 2025, at 7:00 a.m. ET, and a replay will be accessible for 30 days post-event [2]

Core Insights - Passage Bio, Inc. reported updated interim data from the upliFT-D study, indicating that PBFT02 shows robust and durable elevation in cerebrospinal fluid (CSF) progranulin (PGRN) levels and improvement in plasma neurofilament light chain (NfL), a biomarker for disease progression [1][5] - The company has completed dosing of Cohort 2 in the upliFT-D study and submitted an amended protocol to global trial sites and health authorities [2][5] - As of June 30, 2025, the company has a cash position of $57.6 million, which is expected to fund operations into the first quarter of 2027 [4] Recent Highlights - The dosing of Cohort 2 in the upliFT-D study was completed, with a total of four FTD-GRN patients treated [5] - Interim data showed that Dose 1 PBFT02 treatment resulted in a significant increase in CSF PGRN levels, with the first patient treated with Dose 2 showing substantial increases at one month post-treatment [5] - The company plans to initiate enrollment of Cohort 3 (FTD-GRN) and Cohort 4 (FTD-C9orf72) once the amended protocol is approved [2][5] Financial Results - Research and Development (R&D) expenses for Q2 2025 were $5.8 million, down from $10.4 million in Q2 2024 [13] - General and Administrative (G&A) expenses for Q2 2025 were $4.5 million, compared to $6.5 million in Q2 2024 [13] - The net loss for Q2 2025 was $9.4 million, or $2.96 per share, a decrease from a net loss of $16.0 million, or $5.09 per share, in Q2 2024 [13][19] Anticipated Upcoming Milestones - The company seeks regulatory feedback on the suspension-based manufacturing process comparability in the second half of 2025 [5] - Updated interim safety and biomarker data from Dose 2 is expected to be reported in the first half of 2026 [5] - Regulatory feedback on the registrational trial design in FTD-GRN is anticipated in the first half of 2026 [5]

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 Viewpoint - Passage Bio, Inc. is making progress in its clinical trials for PBFT02, a treatment for neurodegenerative diseases, with a focus on frontotemporal dementia (FTD) and plans for future regulatory engagement [2][6]. Recent Highlights - The company treated its first FTD-GRN patient with Dose 2 of PBFT02 and enrolled a second patient, with additional patients being evaluated for trial eligibility [6]. - A high productivity, suspension-based manufacturing process for PBFT02 was presented at the ASGCT 28th Annual Meeting, showing significant improvements in productivity and purity [6]. - The company has a cash runway expected to last into the first quarter of 2027, with cash and cash equivalents totaling $63.4 million as of March 31, 2025 [12]. Anticipated Upcoming Milestones - The company plans to initiate dosing of FTD-C9orf72 patients in the first half of 2025 [4]. - Interim safety and biomarker data from Dose 2 and 12-month data from Dose 1 patients are expected to be reported in the second half of 2025 [6]. Financial Results - For the first quarter of 2025, research and development expenses were $7.7 million, down from $11.5 million in the same quarter of 2024 [12]. - General and administrative expenses decreased to $6.1 million from $6.5 million year-over-year [12]. - The net loss for the quarter was $15.4 million, or $0.25 per share, compared to a net loss of $16.7 million, or $0.30 per share, in the prior year [12][15].

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]