Passage Bio, Inc. · NASDAQ:PASG
Passage Bio — Investor Presentation (November 2024)
30 slides from Passage Bio's investor presentation, Nov 13, 2024
Slide 1: Corporate Presentation November 2024
Nasdaq: PASG © 2024 Passage Bio. All rights reserved. Corporate Presentation November 2024
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 In-house manufacturing process development to support program execution Strong cash position with runway expected to the end of 2Q 2026* Exploring benefits of
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 therapy Proprietary AAV1 construct Nonsurgical in
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 2H 2024 1H 2025 2H 2025 Obtain regulatory feedback on the pathway to treating ALS patients Report 12-month Cohort 1 and interim Cohort 2 data FTD-C9orf72 and ALS Milestones Initiate dosing of FTD-C9orf72 patients Seek regulatory feedback on pivotal
Slide 7: PBFT02 Frontotemporal Dementia-GRN
PBFT02 Frontotemporal Dementia-GRN
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 Pharm 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 elev
Slide 12: Preclinical NHP: ICM Administration Led to Broad Vector Distribution
12 LLoQ Brain Spinal Cord DRG, TRG 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
Slide 13: Preclinical Grn–/– Mice: hPGRN Delivery Improved Lysosomal Dysfunction and Neuroinflammation
13 Preclinical Grn–/– Mice: hPGRN Delivery 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 both
Slide 14: upliFT-D: Global Phase 1/2 Trial with PBFT02
14 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 fiber layer and
Slide 15: Intra-Cisterna Magna (ICM) Administration
15 Intra-Cisterna Magna (ICM) Administration • Directly deliver vector into the CSF via a single injection to reach both CNS and peripheral tissues1 –Allows for broad CNS biodistribution –Lower doses compared to IV systemic delivery –Reduced impact of neutralizing antibodies • Brief (<60 min), non-s
Slide 16: upliFT-D: Interim Data from Cohort Patients
16 upliFT-D: Interim Data from Cohort 1 Patients • PBFT02 was well-tolerated among the four patients (P2-5) who received revised immunosuppression regimen** –Among these patients, there were no SAEs; only mild-to-moderate treatment emergent AEs were reported • No evidence of DRG toxicity, as measure
Slide 17: Initial Patients Treated with PBFT02 Have Seen a Substantial Increase in CSF PGRN
17 • Potential best-in-class PGRN profile at Dose 1 • Continued elevation of CSF PGRN at 6-months (n=2) and 12-months (n=1) –Patient 2 rate of increase slowed between Day 180 and 360 (D30-180: 58% vs. D180-360: 26%) • Consistent response across all treated patients Initial Patients Treated with PBFT
Slide 18: Plasma PGRN Levels Remained Below Normal Levels Post-Dose
18 • Plasma PGRN levels remained below normal levels at up to 12 months post-dose • PGRN increased only in the CSF, where it has potential to correct neurodegeneration Plasma PGRN Levels Remained Below Normal Levels Post-Dose Shading: Lower limit of normal reference range for healthy adult controls’
Slide 19: Summary
19 Summary SAFETY1 PBFT02 Dose 1 generally well-tolerated to date among the four Cohort 1 patients who received revised steroid regimen following protocol amendment • No serious AEs • All AEs mild to moderate in intensity • No evidence of clinically significant immune response, hepatotoxicity or ven
Slide 20: Looking Ahead
Looking Ahead Passage Bio
Slide 21: PBFT02 has Potential to Correct Underlying Pathology in FTD-GRN, FTD-C9orf72 and ALS
21 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 Pharm Sci
Slide 22: Elevated PGRN Ameliorates TDP-43 Pathology in Preclinical Models
22 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 DKO mouse brain TDP-43 pathology in DKO mice reduced by AAV.hPGRN Elevated PGRN reduced insoluble TDP-43
Slide 23: Decreased PGRN Associated with Greater Disease Severity in Multiple CNS Conditions
23 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 (2014) Mol Neurodegen. AD=Alzheimer’s
Slide 24: PBFT02 has Potential to Modulate Alzheimer's Disease
24 • GRN SNP rs5848 carriers have reduced PGRN levels and increased risk for AD • AD patients with GRN SNP rs5848 show reduced PGRN levels and increased CSF tau • GRN SNP rs5848 is estimated to occur in 30% of the general population, with a similar prevalence rate among AD patients2 • PGRN ablation
Slide 25: Leading In-House CMC Capabilities to Support PBFT02 Development
25 Leading In-House CMC Capabilities to Support PBFT02 Development Proven analytical development capabilities In-House CMC Analytical Capabilities to Support Program Advancement and Future Commercialization of PBFT02 Integrated process development GMP QC capabilities Strong regulatory CMC scientific
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 $85 million as of 9/30/24* • Cash runway to the end of 2Q 2026* * Based on cash, cash equivalents and marketable securities and initial proceeds from out-licensi
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 In-house manufacturing process development to support program execution Strong cash position with runway expected to the end of 2Q 2026* Exploring benefits of
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