Slide 1: Corporate Presentation November 2025
Nasdaq: PASG © 2025 Passage Bio. All rights reserved. Corporate Presentation November 2025
Slide 2: Forward-Looking Statement
2 Forward-Looking Statement This presentation includes “forward-looking statements” within the meaning of, and made pursuant to the safe harbor provisions of, the Private Securities Litigation Reform Act of 1995, including, but not limited to: our expectations about timing and execution of anticipat
Slide 3: Redefining the Course of Neurodegenerative Conditions
3 REDEFINING THE COURSE OF NEURODEGENERATIVE CONDITIONS Advancing potential best-in-class, one-time progranulin raising FTD-GRN gene therapy Established suspension-based PBFT02 manufacturing process to support late-stage development Cash runway expected into 1Q 2027* Exploring benefits of elevated p
Slide 4: Validating the Therapeutic Potential of PBFT02
4 Validating the Therapeutic Potential of PBFT02 Promising data from initial clinical study of PBFT02 in FTD-GRN Genetic form of FTD caused by GRN mutations, which lead to progranulin (PGRN) deficiency No approved disease-modifying therapies One-time, gene replacement therapy Proprietary AAV1 constr
Slide 5: Significant Market Opportunity for PBFT02 Across Multiple Neurodegenerative Diseases
5 Significant Market Opportunity for PBFT02 Across Multiple Neurodegenerative Diseases ~18,000 ~21,000 ~72,600 ~3.9M FTD-GRN1–3 FTD-C9orf722–4 AMYOTROPHIC LATERAL SCLEROSIS (ALS) 5–6 ALZHEIMER’S DISEASE (GRN SNP)*7–8 * rs5848 single nucleotide polymorphism (SNP) 1. Greaves CV, et al. J Neurol 2019;
Slide 6: PBFT02 Frontotemporal Dementia
PBFT02 Frontotemporal Dementia
Slide 7: FTD: A Devastating Adult Disease
7 FTD: A Devastating Adult Disease OVERVIEW • Fatal adult-onset neurodegenerative disease affecting the frontal and temporal lobes of the brain, characterized by a decline in behavior, language and executive function • One of the most common causes of early-onset dementia worldwide, disproportionate
Slide 8: Progranulin Deficiency is the Defining Characteristic of FTD-GRN
8 Progranulin Deficiency is the Defining Characteristic of FTD-GRN and Leads to Neurodegeneration Progranulin is critical to maintaining CNS cell homeostasis Rhinn H et al. Trends Pharmacol Sci. 2022, 43:641-652
Slide 9: Elevated PGRN Increases Potential for Improved Cellular Function
9 Elevated PGRN Increases Potential for Improved Cellular Function • Progranulin is a secreted protein that binds to cell membrane receptors to affect multiple intracellular pathways –Major role is regulating intracellular lysosomal activity –Extracellular PGRN is endocytosed via multiple receptors
Slide 10: Preclinical NHP: AAV1 Achieved the Highest Levels of CSF PGRN
10 Preclinical NHP: AAV1 Achieved the Highest Levels of CSF PGRN • AAV1 resulted in superior CSF hPGRN levels, 5x higher than AAV5 and AAVhu68 (an AAV9 variant) vectors, after ICM administration Rhesus macaques (n=2/gp) ICM-delivered AAV.hPGRN (3.3 x 1011 GC/g brain), day 0 *Size and duration of ele
Slide 11: Preclinical NHP: ICM Administration Led to Broad Vector Distribution
11 Preclinical NHP: ICM Administration of PBFT02 Led to Broad Distribution of Vector Throughout Brain/Spinal Cord Vector Biodistribution in NHPs 90 days post-ICM PBFT02 • Robust, dose-dependent vector delivery to cortical and sub-cortical brain regions affected in FTD • NHP low dose, equivalent to c
Slide 12: Preclinical Grn–/– Mice: hPGRN Improved Lysosomal Dysfunction and Neuroinflammation
12 Preclinical Grn–/– Mice: Expression of hPGRN Improved Lysosomal Dysfunction and Neuroinflammation in the Brain Greatest pathological benefit was associated with the highest PGRN levels in the CSF Lipofuscin deposition and microglial activation are hallmark pathologies seen in FTD; Improvements in
Slide 13: upliFT-D: Global Phase 1/2 Trial with PBFT02
13 TRIAL DESIGN upliFT-D: Global Phase 1/2 Trial with PBFT02 Currently enrolling patients in Cohort 3 and Cohort 4 DURATION 2 years; with additional 3 years of follow-up for safety and durability of effect PRIMARY ENDPOINTS Safety and tolerability SECONDARY ENDPOINTS Biomarkers • Progranulin (CSF, p
Slide 14: Intra-Cisterna Magna (ICM) Administration
14 Intra-Cisterna Magna (ICM) Administration • Directly deliver vector into the CSF via a single injection –Allows for broad CNS biodistribution1 –Lower doses compared to IV systemic delivery –Reduced impact of neutralizing antibodies • Brief (<60 min), non-surgical, CT-guided procedure for precise
Slide 15: Key Baseline Demographics for FTD-GRN Participants
15 Key Baseline Demographics for FTD-GRN Participants* Dose 1 (n=7); Dose 2 (n=1) (n=8) Mean / % / n Range Age (yrs) 64.4 51-72 Sex M: 50% F: 50% FTD-GRN phenotype (n) bvFTD: 5 PPA: 3 Disease duration at baseline (yrs) 2.9 1 - 5 PGRN, CSF (ng/mL) 2.1 1.5 - 2.9 PGRN, plasma (ng/mL) 36.6 22.4 - 89.0 N
Slide 16: upliFT-D: PBFT02 Interim Safety Profile
16 upliFT-D: PBFT02 Interim Safety Profile • In 5 of 8 patients, all treatment emergent AEs were mild to moderate in severity • 3 of 8 patients experienced a total of 4 SAEs Dose 1 – Patient 1: asymptomatic venous sinus thrombosis (VST) and hepatotoxicity, leading to a revised immunosuppression regi
Slide 17: PBFT02 Generated Robust, Durable Increases in CSF PGRN in FTD-GRN Patients
17 PBFT02 Generated Robust, Durable Increases in CSF PGRN in FTD-GRN Patients 0 10 20 30 40 0 3 6 9 12 15 18 CSF PGRN, ng/mL Time (months) Progranulin, CSF Dose 1 Dose 2 Data as of June 15, 2025. Mean +/- SEM Shading: Healthy adult sample range for CSF PGRN (range: 3.28 – 8.15 ng/mL, mean: 4.76 ng/m
Slide 18: Plasma NfL Showed Early Evidence of Improvement vs. Natural History
18 Plasma NfL Showed Early Evidence of Improvement in a Disease Progression Biomarker vs. Natural History 29.0% 28.0% 3.7% -15% -10% -5% 0% 5% 10% 15% 20% 25% 30% 35% 40% % Change Plasma NfL Annual Rate of Change Published NHx (n=15) ALLFTD (n=11) PBFT02 (n=4) Data as of June 15, 2025. Mean +/- SEM
Slide 19: PBFT02 Offers Best-in-Class Therapeutic Potential
19 PBFT02 Offers Best-in-Class Therapeutic Potential PBFT02 Product Candidate AAV1 gene therapy delivering GRN AAV9 gene therapy delivering GRN AAV9 gene therapy delivering GRN Stage of Development Phase 1/2 Phase 1/2 Phase 1/2 Route of Administration ICM (Non-surgical, 1 hour procedure) ICM Intrath
Slide 20: PBFT02: Summary of Approach
20 PBFT02: Summary of Approach •AAV delivery of functional GRN gene to express new PGRN, increasing levels both intra- and extra-cellularly –Preserves all natural pathways to properly traffic PGRN intracellularly where it is needed •ICM route of administration enables low doses of AAV and broad CNS
Slide 21: Looking Ahead
Looking Ahead Passage Bio
Slide 22: PBFT02 Has Potential to Correct Underlying Pathology in FTD-GRN, FTD-C9orf72 and ALS
22 PBFT02 has Potential to Correct Underlying Pathology in FTD-GRN, FTD-C9orf72 and ALS TDP-43 pathology is a hallmark of multiple neurodegenerative diseases1 • TDP-43 mislocalizes from nucleus to cytoplasm and forms inclusion bodies 1. Rhinn H et al. Trends Pharmacol Sci. 2022; 43:641-652
Slide 23: Elevated PGRN Ameliorates TDP-43 Pathology in Preclinical Models
23 TDP-43 pathology due to lysosomal dysfunction (GRN/ TMEM106 double knockout, DKO) reduced by AAV.hPGRN1 Elevated PGRN Ameliorates TDP-43 Pathology in Preclinical Models AAV delivered hPGRN to mouse brain TDP-43 pathology in DKO mice reduced by AAV.hPGRN Elevated PGRN reduced insoluble TDP-43 in m
Slide 24: Critical Manufacturing Milestones Achieved to Enable Late-Stage Development
24 Critical Manufacturing Milestones Achieved to Enable Late-Stage Development Functional Potency Assay Developed assay and reached alignment with FDA on suitability of assay for PBFT02 release Robust Manufacturing Process Completed development of high-productivity, suspension-based manufacturing pr
Slide 25: Plan to Initiate Discussions with the FDA on a Registrational Study Design in 1H 2026
25 Plan to Initiate Discussions with the FDA on a Registrational Study Design in 1H 2026 Rationale for a single-arm registrational study • FTD-GRN is a rapidly progressing disease with no approved disease-modifying therapies and a substantial unmet clinical need • Multiple recent gene therapy preced
Slide 26: Upcoming Milestones and Corporate Updates
26 Upcoming Milestones and Corporate Updates PIPELINE • Advancing Huntington’s disease preclinical program BALANCE SHEET • Cash balance of ~$53 million as of 9/30/25* • Cash runway into 1Q 2027 * Based on cash, cash equivalents and marketable securities TIMING MILESTONE 1H 2026 Report updated interi
Slide 27: Redefining the Course of Neurodegenerative Conditions
27 REDEFINING THE COURSE OF NEURODEGENERATIVE CONDITIONS Advancing potential best-in-class, one-time progranulin raising FTD-GRN gene therapy Established suspension-based PBFT02 manufacturing process to support late-stage development Cash runway expected into 1Q 2027* Exploring benefits of elevated
Slide 28: Thank You
Thank You passagebio.com | NASDAQ: PASG
Slide 29: Focused Pipeline Addressing Rare and Prevalent Neurodegenerative Indications
29 Program Indication US/EU prevalence Discovery Preclinical Phase 1/2 Pivotal PBFT02 Frontotemporal dementia - GRN 18,0001-3 Frontotemporal dementia - C9orf72 21,0002-4 Amyotrophic lateral sclerosis 72,6005-6 Alzheimer’s disease with rs5848 SNP 3.9M7-8 Unnamed Huntington’s disease 60,0009 Focused P
Slide 30: Demonstrated Leadership
30 Demonstrated Leadership LEADERSHIP TEAM Deep experience in rare disease, CNS disorders and genetic medicines Eden Fucci SVP Technical Operations BOARD OF DIRECTORS Maxine Gowen, Ph.D. Chairwoman Athena Countouriotis, M.D. Avenzo Therapeutics Derrell Porter, M.D. cTRL Therapeutics Dolan Sondhi, Ph