Passage Bio, Inc. · NASDAQ:PASG
Passage Bio — Investor Presentation (January 2026)
35 slides from Passage Bio's investor presentation, Jan 12, 2026
Slide 1: Corporate Presentation: Redefining the Course of Neurodegenerative Conditions
© 2026 Passage Bio. All rights reserved. Corporate Presentation Redefining the Course of Neurodegenerative Conditions January 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 anticip
Slide 3: Redefining the Course of Neurodegenerative Conditions
January 2026 3 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 di
Slide 4: Validating the Therapeutic Potential of PBFT02
Validating the Therapeutic Potential of PBFT02 January 2026 4 * 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 cau
Slide 5: Significant Market Opportunity Addressing Neurodegenerative Diseases
Significant Market Opportunity Addressing Neurodegenerative Diseases Estimated Prevalence (US and EU) January 2026 5 Huntington’s disease 5 FTD - C9orf72 2 – 4 FTD - GRN 1 – 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.
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
Slide 8: Progranulin Deficiency is the Defining Characteristic of FTD-GRN
Progranulin Deficiency is the Defining Characteristic of FTD - GRN and Leads to Neurodegeneration January 2026 8 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,
Slide 9: Elevated PGRN Increases Potential for Improved Cellular Function
Elevated PGRN Increases Potential for Improved Cellular Function January 2026 9 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 CN
Slide 10: Preclinical NHP: AAV1 Achieved the Highest Levels of CSF PGRN
Preclinical NHP: AAV1 Achieved the Highest Levels of CSF PGRN January 2026 10 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 - de
Slide 11: Preclinical NHP: Broad Distribution of Vector Throughout Brain/Spinal Cord
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
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 January 2026 12 Greatest pathological benefit was associated with the highest PGRN levels in the CSF Lipofuscin deposition and microglial activation are hallmark pathologies seen in FTD;
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 January 2026 13 2 years; with additional 3 years of follow - up for safety and durability of effect DURATION Safety and tolerability PRIMARY ENDPOINTS Biomarkers • Progranulin (CSF, plas
Slide 14: Intra-Cisterna Magna (ICM) Administration
Cisterna magna Intra - Cisterna Magna (ICM) Administration January 2026 14 Directly deliver vector into the CSF via a single injection • Allows for broad CNS biodistribution 1 • Lower doses compared to IV systemic delivery • Reduced impact of neutralizing antibodies Brief (<60 min), non - surgical,
Slide 15: Key Baseline Demographics for FTD-GRN Participants
Key Baseline Demographics for FTD - GRN Participants* Dose 1 (n=7); Dose 2 (n=1) Range Mean / % / n (n=8) 51 – 72 64.4 Age (yrs) M: 50% F: 50% Sex bvFTD : 5 PPA: 3 FTD - GRN phenotype (n) 1 – 5 2.9 Disease duration at baseline (yrs) 1.5 – 2.9 2.1 PGRN, CSF (ng/mL) 22.4 – 89.0 36.6 PGRN, plasma (ng/m
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
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 available 1,3 • PBFT02 - treated patients with 12 months follow - up (n=4) had a reduced annu
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 AAV9 gene therapy delivering GRN AAV9 gene therapy delivering GRN AAV1 gene therapy delivering GRN Product Candidate Phase 1/2 Phase 1/2 Phase 1/2 Stage of Development Intrathalamic (neurosurgery, lengthy procedure) ICM ICM (non - surgical
Slide 20: PBFT02 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 January 2026 20 TDP - 43 pathology is a hallmark of multiple neurodegenerative diseases 1 • TDP - 43 mislocalizes from nucleus to cytoplasm • Forms inclusion bodies associated with neurodegeneration
Slide 21: Elevated PGRN Ameliorates TDP-43 Pathology in Preclinical Models
Elevated PGRN Ameliorates TDP - 43 Pathology in Preclinical Models January 2026 21 TDP - 43 pathology due to lysosomal dysfunction ( GRN / TMEM106 double knockout, DKO) reduced by AAV.hPGRN 1 AAV delivered hPGRN to mouse brain TDP - 43 pathology in DKO mice reduced by AAV.hPGRN Elevated PGRN reduced
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 - s
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 US 1 CLINICAL SYMPTOMS • Symptom ons
Slide 25: HD Is Caused By A Mutation In the 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 ) January 2026 25 Normal huntingtin gene, HTT , CAG </= 35 Mutant huntingtin gene, mHTT , CAG > 35 GLUTAMINES Exon 1
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 January 2026 27 Developing a differentiated approach to decrease MSH3 expression via AAV delivery of a miRNA Proof - of - concept studies completed, with additio
Slide 28: Looking Ahead
Looking Ahead r | 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 doses 1 with >70% full capsids Robust Manufacturing Process Aligned with the FDA on an analytical approach to establish comparability of suspension - based process P
Slide 30: Plan to Initiate Discussions with the FDA on a Registrational Study Design in 1H 2026
1 FTD - GRN is a rapidly progressing disease with no approved disease - modifying therapies and a substantial unmet clinical need 2 Multiple recent gene therapy precedents demonstrate FDA receptivity to a single - arm registrational approach 3 Existing, well - structured FTD natural history studies
Slide 31: Upcoming Milestones and Corporate Updates
Upcoming Milestones and Corporate Updates BALANCE SHEET • Cash balance of ~$46 million as of 12/31/25* • Cash runway into 1Q 2027 * Based on cash, cash equivalents and marketable securities. MILESTONE TIMING Report updated interim safety and biomarker data from Dose 2 in FTD patients 1H 2026 Seek re
Slide 32: Redefining the Course of Neurodegenerative Conditions
January 2026 32 * 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 di
Slide 33: Thank you!
© 2026 Passage Bio. All rights reserved. passagebio.com Thank you!
Slide 34: Focused Pipeline Addressing Rare and Prevalent Neurodegenerative Indications
Pivotal Phase 1/2 Preclinical Discovery US/EU prevalence Indication Program 18,000 1 - 3 Frontotemporal dementia — GRN PBFT02 21,000 2 - 4 Frontotemporal dementia — C9orf72 72,600 5 - 6 Amyotrophic lateral sclerosis 3.9M 7 - 8 Alzheimer’s disease with rs5848 SNP 70,000 9 Huntington’s disease Unnamed
Slide 35: Leadership Team and Board of Directors
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