Passage Bio, Inc. · NASDAQ:PASG
Passage Bio — Investor Presentation (March 2026)
34 slides from Passage Bio's investor presentation, Mar 3, 2026
Slide 1: Redefining the Course of Neurodegenerative Conditions
© 2026 Passage Bio. All rights reserved. Corporate Presentation Redefining the Course of Neurodegenerative Conditions March 2026
Slide 2: Forward-Looking Statement
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 anticipated
Slide 3: Redefining the Course of Neurodegenerative Conditions
3 March 2026 Redefining the Course of Neurodegenerative Conditions * Based on cash, cash equivalents, and marketable securities as of December 31, 2025. Advancing clinical stage, potential best-in-class, one-time progranulin raising gene therapy for FTD Pursuing preclinical development of differenti
Slide 4: Validating the Therapeutic Potential of PBFT02
Validating the Therapeutic Potential of PBFT02 4 March 2026 * Based on interim data. Urgent Patient Need in FTD-GRN Differentiated, Potential Best-in-Class Profile Fast Track and Orphan Drug Designation Promising data from initial clinical study of PBFT02 in FTD-GRN Genetic form of FTD caused by GRN
Slide 5: Significant Market Opportunity Addressing Neurodegenerative Diseases
Significant Market Opportunity Addressing Neurodegenerative Diseases Estimated Prevalence (US and EU) 5 March 2026 Huntington’s disease5 FTD-C9orf722–4 FTD-GRN1–3 ~18K ~21K ~70K 1. Greaves CV, et al. J Neurol 2019; 266:2075-2086. 2. Galvin JE, et al. Neurology 2017; 89:2049-2056. 3. Onyike CU, et al
Slide 6: PBFT02 Frontotemporal Dementia
PBFT02 Frontotemporal Dementia
Slide 7: Frontotemporal Dementia (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, disproportionately affecting individuals aged 40–6
Slide 8: Progranulin Deficiency is the Defining Characteristic of FTD-GRN
Progranulin Deficiency is the Defining Characteristic of FTD-GRN and Leads to Neurodegeneration 8 March 2026 Progranulin is critical to maintaining CNS cell homeostasis Rhinn H et al. Trends Pharmacol Sci. 2022, 43:641-652. Decrease in PGRN levels Neuronal dysfunction, pathological changes, and infl
Slide 9: Elevated PGRN Increases Potential for Improved Cellular Function
Elevated PGRN Increases Potential for Improved Cellular Function 9 March 2026 Paushter et al. Acta Neuropathol. 2018;136:1-17. Rhinn et al. Trends Pharmacol Sci. 2022; 43:641-652. Driving elevated PGRN levels in the extracellular space increases the amount of PGRN available to enter target CNS cells
Slide 10: Preclinical NHP: AAV1 Achieved the Highest Levels of CSF PGRN
Preclinical NHP: AAV1 Achieved the Highest Levels of CSF PGRN 10 March 2026 After ICM administration to NHPs: • AAV1 capsid resulted in CSF hPGRN levels 5x higher than AAVhu68 (an AAV9 variant) • Superior hPGRN response led to selection of AAV1 capsid for PBFT02 Rhesus macaques (n=2/gp) ICM-delivere
Slide 11: Preclinical NHP: ICM Administration Led to Broad Vector Distribution
Preclinical NHP: ICM Administration of PBFT02 Led to Broad Distribution of Vector Throughout Brain/Spinal Cord • Robust, dose-dependent vector delivery to cortical and sub-cortical brain regions affected in FTD • NHP low dose, equivalent to clinical Dose 1 of PBFT02 in upliFT-D study, resulted in ~1
Slide 12: Preclinical Grn–/– Mice: hPGRN Improved Lysosomal Dysfunction and Neuroinflammation
Preclinical Grn–/– Mice: Expression of hPGRN Improved Lysosomal Dysfunction and Neuroinflammation in the Brain 12 March 2026 Greatest pathological benefit was associated with the highest PGRN levels in the CSF Lipofuscin deposition and microglial activation are hallmark pathologies seen in FTD; Impr
Slide 13: upliFT-D: Global Phase 1/2 Trial with PBFT02
TRIAL DESIGN upliFT-D: Global Phase 1/2 Trial with PBFT02 Currently enrolling patients in Cohort 3 and Cohort 4 13 March 2026 DURATION 2 years; with additional 3 years of follow-up for safety and durability of effect PRIMARY ENDPOINTS Safety and tolerability SECONDARY ENDPOINTS Biomarkers • Progranu
Slide 14: Intra-Cisterna Magna (ICM) Administration
Cisterna magna Intra-Cisterna Magna (ICM) Administration 14 March 2026 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-guid
Slide 15: Key Baseline Demographics for FTD-GRN Participants
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 NfL, pl
Slide 16: PBFT02 Generated Robust, Durable Increases in CSF PGRN in FTD-GRN Patients
Healthy adult range 0 10 20 30 40 0 3 6 9 12 15 18 CSF PGRN, ng/mL Time (months) Dose 1 Dose 2 Progranulin, CSF PBFT02 Generated Robust, Durable Increases in CSF PGRN in FTD-GRN Patients Data as of June 15, 2025. Mean +/- SEM Shading: Healthy adult sample range for CSF PGRN (range: 3.28 – 8.15 ng/mL
Slide 17: Plasma NfL Showed Early Evidence of Improvement vs. Natural History
Plasma NfL Showed Early Evidence of Improvement in a Disease Progression Biomarker vs. Natural History • Plasma NfL is the only FTD-GRN disease progression biomarker with longitudinal natural history data available1,3 • PBFT02-treated patients with 12 months follow-up (n=4) had a reduced annual rate
Slide 18: PBFT02 Interim Safety Profile
PBFT02 Interim Safety Profile PBFT02 was generally well tolerated • SAEs related to PBFT02 all asymptomatic; all occurred at Dose 1 • Venous sinus thrombosis (2) • LFT increase (1) • No SAEs related to PBFT02 at Dose 2 • No evidence of thrombotic microangiopathy • No evidence of dorsal root ganglion
Slide 19: PBFT02 Offers Best-in-Class Therapeutic Potential
PBFT02 Offers Best-in-Class Therapeutic Potential PBFT02 Product Candidate AAV1 gene therapy delivering GRN AAV9 gene therapy delivering GRN PGRN replacement therapy via protein transport vehicle Stage of Development Phase 1/2 Phase 1/2 Phase 1/2 Route of Administration ICM (non-surgical, 1 hour pro
Slide 20: PBFT02 has Potential to Correct Underlying Pathology in FTD-GRN, FTD-C9orf72 and ALS
PBFT02 has Potential to Correct Underlying Pathology in FTD-GRN, FTD-C9orf72 and ALS 20 March 2026 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. Trend
Slide 21: Elevated PGRN Ameliorates TDP-43 Pathology in Preclinical Models
Elevated PGRN Ameliorates TDP-43 Pathology in Preclinical Models 21 March 2026 TDP-43 pathology due to lysosomal dysfunction (GRN/ TMEM106 double knockout, DKO) reduced by AAV.hPGRN1 AAV delivered hPGRN to mouse brain TDP-43 pathology in DKO mice reduced by AAV.hPGRN Elevated PGRN reduced insoluble
Slide 22: 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 biodistribution • Non-surgic
Slide 23: Huntington's Disease Preclinical Program
Huntington’s Disease Preclinical Program
Slide 24: Huntington's Disease: A Fatal Neurodegenerative Disease with No Disease-Modifying Therapy
OVERVIEW • Fatal, monogenic, autosomal dominant neurodegenerative disease • Caused by trinucleotide (CAG) expansion in the huntingtin (HTT) gene resulting in mutant huntingtin (mHTT) protein expression • More than 200,000 people estimated to be at risk in the US1 CLINICAL SYMPTOMS • Symptom onset ty
Slide 25: HD Is Caused By A Mutation In Huntingtin (HTT) Gene
Unaffected HD Is Caused By A Mutation In Huntingtin (HTT) Gene: A Stretch Of CAG Nucleotides Is Expanded CAG repeat expansion leads to production of mutant huntingtin protein (mHTT) 25 March 2026 Normal huntingtin gene, HTT, CAG </= 35 Mutant huntingtin gene, mHTT, CAG > 35 GLUTAMINES Exon 1 Exons 2
Slide 26: DNA Repair Proteins Play a Key Role in CAG Repeat Expansion
DNA Repair (DR) Proteins Play a Key Role in CAG Repeat Expansion • CAG expansion above a certain threshold leads to neurodegeneration • Longer CAG repeats associated with worse disease pathology • CAG expansion occurs at different rates in different neurons, and is fastest in the caudate and putamen
Slide 27: Our Approach: Decrease MSH3 to Reduce Somatic Instability in the HTT Gene
Program Status Our Approach: Decrease MSH3 to Reduce Somatic Instability in the HTT Gene Expect to declare a clinical candidate in 2H 2026 27 March 2026 Developing a differentiated approach to decrease MSH3 expression via AAV delivery of a miRNA Proof-of-concept studies completed, with additional pr
Slide 28: Looking Ahead
Looking Ahead aff PassageBio
Slide 29: Critical Manufacturing Milestones Achieved to Enable Late-Stage Development of PBFT02
Completed development of high-productivity, suspension-based manufacturing process Single production lot estimated to yield >1,000 doses1 with >70% full capsids Robust Manufacturing Process Aligned with the FDA on an analytical approach to establish comparability of suspension-based process Process
Slide 30: Upcoming Milestones and Corporate Updates
Upcoming Milestones and Corporate Updates BALANCE SHEET • Cash balance of ~$46 million as of 12/31/25* • Cash runway through 1Q 2027 * Based on cash, cash equivalents and marketable securities. TIMING MILESTONE 1H 2026 Report updated interim safety and biomarker data from Dose 2 in FTD patients 1H 2
Slide 31: Redefining the Course of Neurodegenerative Conditions
31 March 2026 * Based on cash, cash equivalents and marketable securities as of December 31, 2025. Redefining the Course of Neurodegenerative Conditions Advancing clinical stage, potential best-in-class, one-time progranulin raising gene therapy for FTD Pursuing preclinical development of differenti
Slide 32: Thank you!
© 2026 Passage Bio. All rights reserved. passagebio.com Thank you!
Slide 33: Focused Pipeline Addressing Rare and Prevalent Neurodegenerative Indications
Program Indication US/EU prevalence Discovery Preclinical Phase 1/2 Pivotal PBFT02 Frontotemporal dementia — GRN 18,0001-3 Frontotemporal dementia — C9orf72 21,0002-4 Unnamed Huntington’s disease 70,0005 Focused Pipeline Addressing Rare and Prevalent Neurodegenerative Indications 1. Greaves CV, et a
Slide 34: Demonstrated Leadership
LEADERSHIP TEAM Demonstrated Leadership BOARD OF DIRECTORS Maxine Gowen, Ph.D. Chairwoman Athena Countouriotis, M.D. Avenzo Therapeutics Derrell Porter, M.D. cTRL Therapeutics Dolan Sondhi, Ph.D. Weill Cornell Medicine Sandip Kapadia Harmony Biosciences Thomas Kassberg Former CBO Ultragenyx William