Slide 1: Corporate Presentation May 2025
Nasdaq: PASG © 2025 Passage Bio. All rights reserved. Corporate Presentation May 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 Strong cash position with runway expected to the end of 1Q 2027* Ex
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: Anticipated Upcoming Milestones and Data Readouts
6 Anticipated Upcoming Milestones and Data Readouts 1H 2025 2H 2025 1H 2026 Report 12-month Dose 1 and interim Dose 2 data FTD-C9orf72 Initiate dosing of FTD-C9orf72 patients Seek regulatory feedback on registrational trial design FTD-GRN Milestones
Slide 7: PBFT02 Frontotemporal Dementia
PBFT02 Frontotemporal Dementia
Slide 8: FTD: A Devastating Adult Disease
8 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 9: Progranulin Deficiency is the Defining Characteristic of FTD-GRN
9 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 10: Elevated PGRN Increases Potential for Improved Cellular Function
10 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 11: Preclinical NHP: AAV1 Achieved the Highest Levels of CSF PGRN
11 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 12: Preclinical NHP: Broad Distribution of Vector Throughout Brain/Spinal Cord
12 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 13: Preclinical Grn–/– Mice: hPGRN Improved Lysosomal Dysfunction and Neuroinflammation
13 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 14: upliFT-D: Global Phase 1/2 Trial with PBFT02
14 TRIAL DESIGN upliFT-D: Global Phase 1/2 Trial with PBFT02 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, plasma) • GFAP (CSF, plasma) • vMRI • Retinal nerve fib
Slide 15: Intra-Cisterna Magna (ICM) Administration
15 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 16: upliFT-D: Interim Safety Profile
16 upliFT-D: Interim Safety Profile • In 5 of 7 patients, all treatment emergent AEs were mild to moderate in severity • 2 of 7 patients experienced a total of 3 SAEs – Patient 1: asymptomatic venous sinus thrombosis (VST) and hepatotoxicity, leading to a revised immunosuppression regimen in all sub
Slide 17: PBFT02 Generated Robust, Durable Increases in CSF PGRN
17 PBFT02 Generated Robust, Durable Increases in CSF PGRN Shading: Healthy adult sample range for CSF PGRN (range: 3.28 – 8.15 ng/mL, mean: 4.76 ng/mL, n = 61) (Passage Bio data) CSF, cerebrospinal fluid 0 10 20 30 40 0 1 6 12 18 CSF PGRN, ng/mL Time (months) Dose 1 Progranulin, CSF P1 P2 P3 P4 P5 P
Slide 18: Plasma PGRN Levels Remained Below Normal Levels Post-Dose
18 • Plasma PGRN levels remained below normal levels up to 12 months post-dose in FTD-GRN patients • PGRN increased only in the CSF, where it has potential to reduce neurodegeneration Plasma PGRN Levels Remained Below Normal Levels Post-Dose Shading: Lower limit of healthy adult sample range for pla
Slide 19: Plasma NfL Showed Early Evidence of Improvement vs. Natural History
19 Plasma NfL Showed Early Evidence of Improvement in a Disease Progression Biomarker vs. Natural History 29.0% -15% -12.7% -10% -5% 0% 5% 10% 15% 20% 25% 30% 35% % Change Plasma NfL Annual Rate of Change Natural History (n=15) PBFT02 (n=2) Baseline plasma NfL (neurofilament light chain) range: 39.6
Slide 20: PBFT02 Offers Best-in-Class Therapeutic Potential
20 PBFT02 Offers Best-in-Class Therapeutic Potential PBFT02 Product Candidate AAV1 gene therapy delivering GRN Anti-sortilin antibody AAV9 gene therapy delivering GRN Stage of Development Phase 1/2 Phase 3 Phase 1/2 Route of Administration ICM IV ICM Expected Frequency of Administration One Time Mon
Slide 21: Summary: FTD-GRN
21 Summary: FTD-GRN SAFETY1 PBFT02 Dose 1 •In 5 of 7 patients, all treatment emergent AEs were mild to moderate • 2 of 7 patients experienced a total of 3 SAEs •No evidence of clinically significant immune response following introduction of new immunosuppression regimen •No evidence of DRG toxicity
Slide 22: Looking Ahead
Looking Ahead Passage Bio
Slide 23: PBFT02 Potential to Correct Underlying Pathology in FTD-GRN, FTD-C9orf72 and ALS
23 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 • Forms inclusion bodies associated with neurodegeneration 1. Rhinn H et al. Trends Pharmacol
Slide 24: Elevated PGRN Ameliorates TDP-43 Pathology in Preclinical Models
24 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 25: Decreased PGRN Associated with Greater Disease Severity in Multiple CNS Conditions
25 GRN rs5848 SNP associated with accelerated disease in FTD-C9orf72 patients Decreased PGRN Associated with Greater Disease Severity in Multiple CNS Conditions GRN rs5848 SNP associated with accelerated disease in FTD-C9orf72 patients 1. van Blitterswijk et al. Mol Neurodegen. 2014; 9:38 AD, Alzhei
Slide 26: Critical Manufacturing Milestones Achieved to Enable Late-Stage Development
26 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 27: Upcoming Milestones and Corporate Updates
27 Upcoming Milestones and Corporate Updates PIPELINE • Advancing Huntington’s disease preclinical program BALANCE SHEET • Cash balance of ~$63 million as of 3/31/25* • Cash runway into 1Q 2027 * Based on cash, cash equivalents and marketable securities TIMING MILESTONE FTD-GRN 2H 2025 Report 12-mon
Slide 28: Redefining the Course of Neurodegenerative Conditions
28 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 Strong cash position with runway expected to the end of 1Q 2027* E
Slide 29: Thank You
Thank You passagebio.com | NASDAQ: PASG
Slide 30: Focused Pipeline Addressing Rare and Prevalent Neurodegenerative Indications
30 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 31: Demonstrated Leadership
31 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