Passage Bio, Inc. · NASDAQ:PASG
Passage Bio — Investor Presentation (January 2024)
28 slides from Passage Bio's investor presentation, January 2024
Slide 1: Corporate Presentation
Corporate Presentation January 2024 Nasdaq: PASG © 2024 Passage Bio. All rights reserved.
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: Our Vision
Potential best in class progranulin raising FTD-GRN gene therapy program Our Vision To improve patient lives with neurodegenerative Portfolio expansion into additional adult neurodegenerative diseases diseases by delivering genetic medicines that will permanently redefine the Established manufacturi
Slide 4: Pipeline with Potential to Address Multiple Neurodegenerative Diseases
Pipeline with Potential to Address Multiple Neurodegenerative Diseases US/EU Program Indication Discovery Pre-clinical Phase 1/2 Pivotal prevalence Frontotemporal dementia - 18,0001-3 GRN Frontotemporal dementia - 21,0002-4 C9orf72 PBFT02 Amyotrophic lateral sclerosis 72,6005-6 Alzheimer’s disease w
Slide 5: Lead Clinical Program: PBFT02 Has Demonstrated Best in Class Potential in FTD-GRN
Lead Clinical Program: PBFT02 Has Demonstrated Best in Class Potential in FTD-GRN Global Dose-Escalation Study of Differentiated, Potential PBFT02 in FTD-GRN Best in Class Product Profile Initial Data from First 3 Treated Patients • One time therapy • Supraphysiologic CSF PGRN levels 4x-7x • Durable
Slide 6: Leading CMC Capabilities Via a Hybrid Approach
Leading CMC Capabilities Via a Hybrid Approach Critical analytical and development capabilities maintained in-house Process/Analytic External Development Manufacturing Partnerships and GMP Passage CMC R&D Lab End-to-End Supply Chain Manufacturing Proven Analytical Capabilities Discovery Longstanding
Slide 7: PBFT02 Frontotemporal Dementia — GRN
PBFT02 Frontotemporal Dementia — GRN
Slide 8: FTD-GRN: A Devastating Adult Disease
FTD-GRN: A Devastating Adult Disease OVERVIEW • Devastating form of dementia caused by a GRN gene mutation resulting in progranulin (PGRN) deficiency and haploinsufficiency • No disease-modifying therapies are currently approved CLINICAL SYMPTOMS • Disease progression is rapid and degenerative inclu
Slide 9: Progranulin Deficiency is the Defining Characteristic of FTD-GRN and Leads to Neurodegeneration
Progranulin Deficiency is the Defining Characteristic of FTD-GRN and Leads to Neurodegeneration Progranulin is critical to maintaining CNS cell homeostasis 9 Source: Rhinn H et al. Trends Pharm Sci. 2022, 43:641-652
Slide 10: PBFT02
PBFT02 Potential transformative therapy • Proprietary AAV1 construct delivering functional GRN gene encoding progranulin (PGRN) • Potential therapeutic benefit of a one-time approach • Delivered directly to the CSF via a single intra-cisterna magna (ICM) injection: – Allows for broad CNS biodistribu
Slide 11: Preclinical: PBFT02 Achieved Supraphysiologic Levels of CSF Progranulin in NHPs
Preclinical: PBFT02 Achieved Supraphysiologic Levels of CSF Progranulin in NHPs • AAV1 increased CSF PGRN levels ~5x more than AAV5 and AAVhu68 vectors, without further elevating peripheral levels AAV1 transgene delivery led to Production of Human supraphysiologic hPGRN levels in CSF RA2981 RA2982 A
Slide 12: Supraphysiologic PGRN Increases Potential for Improved Cellular Function
Supraphysiologic 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 progranulin is endocytosed via mult
Slide 13: Preclinical: Higher CSF PGRN May Confer Reduction in Inflammatory Response
Preclinical: Higher CSF PGRN May Confer Reduction in Inflammatory Response PBFT02 reduced lipofuscin at all doses, Microgliosis reduction strongest at highest suggesting correction of underlying mechanism PBFT02 dose / PGRN level of disease Murine FTD Model Murine FTD Model • Lipofuscin: increased l
Slide 14: Preclinical: PBFT02 Showed Dose-Related Increases in CSF Progranulin in NHPs
Preclinical: PBFT02 Showed Dose-Related Increases in CSF Progranulin in NHPs Human PGRN Levels in CSF of NHPs 14 days post-ICM Dose Equivalent Clinical Dose Vehicle Dose 1 Low Dose Dose 2 Medium Dose Dose 3 (optional) High Dose 0 2 4 6 8 10 12 Human PGRN (ng/ml) • NHP immune response to hPGRN limits
Slide 15: upliFT-D: Global Phase 1/2 Trial with PBFT02
upliFT-D: Global Phase 1/2 Trial with PBFT02 Phase 1/2, multicenter, open-label, dose escalation Trial Design study; up to 15 patients across 3 cohorts OPTIONAL COHORT 3 2 years; with additional 3 years of follow-up Duration for safety and durability of effect Primary OPTIONAL DOSE 3 • Safety and to
Slide 16: upliFT-D: Interim Data from First 3 Treated Patients
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 & Patient 3 received a higher level of steroid immunosuppression and did Safety* not experience SAEs; only mild
Slide 17: Following Protocol Update to Increase Steroids, Patients 2 & 3 had no SAEs
Following Protocol Update to Increase Steroids, Patients 2 & 3 had no SAEs or Evidence of Significant Immune Response Patient 1 Patient 2 Patient 3 Days 1-3: 1,000 mg IV methylprednisolone Immunosuppression1 Day -1-60: 60 mg oral prednisone Days 4-60: 60 mg oral prednisone Day 14-21 and Day 51-55: e
Slide 18: Initial Patients Treated with PBFT02 Have Seen a Substantial Increase in CSF PGRN
Initial Patients Treated with PBFT02 Have Seen a Substantial Increase in CSF PGRN CSF Progranulin (ng/mL) Dose 1 Progranulin, CSF Italics – fold increase At Dosing D30 D180 vs. baseline 30 Patient 1 1.9 12.7 N/A 9.9x 27 Patient 2 2.8 17.3 27.3 24 Patient 3 2.9 10.7 N/A 21 • Dose 1 resulted in suprap
Slide 19: Plasma PGRN Levels Remained Below Normal Levels Post-Dose
Plasma PGRN Levels Remained Below Normal Levels Post-Dose Dose 1 Progranulin, Plasma 100 90 80 • Plasma PGRN levels remained below normal levels at up to 6-months post-dose Plasma PGRN, ng/mL 70 60 • PGRN increased only in the CSF where it 50 has potential to correct deficit associated 40 with neuro
Slide 20: Summary
Summary SAFETY* BIOMARKERS ANTICIPATED PBFT02 Dose 1 generally well- Evidence of target NEXT STEPS tolerated to date in Patients 2 engagement with 3.6-6.6-fold & 3, who received revised • Initiate dosing of Cohort 2 increase in CSF progranulin in patients in 1H 2024 steroid regimen following all par
Slide 21: Looking Ahead
Looking Ahead PassageBio
Slide 22: 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 TDP-43 pathology is a hallmark of multiple Supraphysiologic PGRN neurodegenerative diseases1 ameliorates TDP-43 pathology in • TDP-43 mislocalizes from nucleus to cytoplasm • Forms inclusion bodies associated with
Slide 23: PBFT02 has Potential to Modulate Alzheimer's Disease
PBFT02 has Potential to Modulate Alzheimer’s Disease • GRN SNP rs5848 carriers have reduced PGRN levels and increased risk for AD Genetic risk1 • AD patients with GRN SNP rs5848 show reduced PGRN levels and increased CSF tau • GRN SNP rs5848 is estimated to occur in 30% of general population, with a
Slide 24: Upcoming Milestones and Corporate Updates
Upcoming Milestones and Corporate Updates PIPELINE TIMING MILESTONE • Pursuing potential partnerships to advance pediatric clinical-stage FTD-GRN 1H 2024 Initiate dosing of Cohort 2 patients programs (GM1, Krabbe & MLD) • Prioritizing advancement of 6-month safety and biomarker data from Huntington’
Slide 25: Our Vision
Potential best in class progranulin raising FTD-GRN gene therapy program Our Vision To improve patient lives with neurodegenerative Portfolio expansion into multiple adult neurodegenerative diseases diseases by delivering genetic medicines that will permanently redefine the Established manufacturing
Slide 26: Thank You
Thank You passagebio.com | NASDAQ: PASG
Slide 27: Demonstrated Leadership
Demonstrated Leadership Deep experience in rare disease, CNS disorders and genetic medicines LEADERSHIP TEAM BOARD OF DIRECTORS Maxine Gowen, Ph.D. Chairwoman Athena Countouriotis, M.D. Avenzo Therapeutics Derrell Porter, M.D. William Chou, M.D. Kathleen Borthwick Chip Cale cTRL Therapeutics Preside
Slide 28: Intra-Cisterna Magna (ICM) Administration
Intra-Cisterna Magna (ICM) Administration • Directly deliver vector into the CSF via a single injection to reach both CNS and peripheral tissues* – Allows for broad CNS biodistribution – Lower doses compared to IV systemic delivery – Reduced impact of neutralizing antibodies • Administered under ane