Passage Bio, Inc. · NASDAQ:PASG
Passage Bio — Investor Presentation (May 2024)
30 slides from Passage Bio's investor presentation, May 14, 2024
Slide 1: Corporate Presentation May 2024
Nasdaq: PASG © 2024 Passage Bio. All rights reserved. Corporate Presentation May 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 and process analytics to support program execution Strong cash position with runway expected into 4Q 2025* Exploring benefits of elevate
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 1H 2024 2H 2024 1H 2025 Initiate dosing of Cohort 2 FTD-GRN patients Obtain regulatory feedback on the pathway to treating FTD-C9orf72 and ALS patients Report 6-month safety and biomarker data from Cohort 1 patients Announce 12-month follow-up data
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: AAV1 Achieved the Highest Levels of CSF PGRN in NHPs
11 Preclinical: AAV1 Achieved the Highest Levels of CSF PGRN in NHPs AAV1 increased CSF PGRN levels ~5x more than AAV5 and AAVhu68 (proprietary AAV9 variant) vectors, without further elevating peripheral levels Production of Human PGRN in Plasma AAV1 transgene delivery led to highest hPGRN levels in
Slide 12: Preclinical: Higher CSF PGRN May Confer Reduction in Inflammatory Response
12 Preclinical: Higher CSF PGRN May Confer Reduction in Inflammatory Response • Microgliosis: inflammatory response to pathogenic insults in the CNS • CD68: marker of activated microglia Thalamus data shown above. Thalamic atrophy is a key feature commonly found in FTD PBFT02 reduced lipofuscin at a
Slide 13: upliFT-D: Global Phase 1/2 Trial with PBFT02
13 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 14: Intra-Cisterna Magna (ICM) Administration
14 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 15: upliFT-D: Interim Data from First Treated Patients
15 upliFT-D: Interim Data from First 3 Treated Patients • Patient 1 experienced two SAEs consistent with an immune response; study protocol was revised to increase steroid regimen • Patient 2 and Patient 3 received a higher level of steroid immunosuppression and did not experience SAEs; only mild-to
Slide 16: Following Protocol Update to Increase Steroids, Patients 2 and 3 Had No SAEs
16 Following Protocol Update to Increase Steroids, Patients 2 and 3 Had No SAEs or Evidence of Significant Immune Response Patient 1 Patient 2 Patient 3 Immunosuppression1 Days -1-60: 60 mg oral prednisone Days 1-3: 1,000 mg IV methylprednisolone Days 4-60: 60 mg oral prednisone Length of Follow-up
Slide 17: Initial Patients 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) • Consistent response across first three treated patients Initial Patients Treated with PBFT02 Have Seen a Substantial Increase in CSF PGRN At Dosing D30 D60 D180 Patient 1 1.9 12.7 N/A N/A Patien
Slide 18: Plasma PGRN Levels Remained Below Normal Levels Post-Dose
18 • Plasma PGRN levels remained below normal levels at up to 6 months post-dose • PGRN increased only in the CSF where it has potential to correct deficit associated with neurodegeneration Plasma PGRN Levels Remained Below Normal Levels Post-Dose Shading: Lower limit of normal reference range for h
Slide 19: Summary
19 Summary SAFETY1 PBFT02 Dose 1 generally well-tolerated to date in Patients 2 and 3, 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 venous sinus th
Slide 20: Looking Ahead
Looking Ahead Passage Bio
Slide 21: PBFT02 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 TIMING MILESTONE FTD-GRN 1H 2024 Initiate dosing of Cohort 2 patients 2H 2024 6-month safety and biomarker data from Cohort 1 patients 1H 2025 12-month follow-up data from Cohort 1 patients 1H 2025 Initial safety and biomarker data from Cohort 2 patients PBFT02 Additional Indications 2H 2024 Obta
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 and process analytics to support program execution Strong cash position with runway expected into 4Q 2025* Exploring benefits of elevat
Slide 28: Thank You
Thank You passagebio.com | NASDAQ: PASG
Slide 29: Focused Pipeline Addressing Rare and Prevalent Neurodegenerative Indications
29 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 Amyotrophic lateral sclerosis 72,6005-6 Alzheimer’s d
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