Passage Bio, Inc. · NASDAQ:PASG
Passage Bio — Investor Presentation (March 2024)
28 slides from Passage Bio's investor presentation, Mar 4, 2024
Slide 1: Corporate Presentation March 2024
Nasdaq: PASG © 2024 Passage Bio. All rights reserved. Corporate Presentation March 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: Our Vision
3 Our Vision To improve patient lives with neurodegenerative diseases by delivering genetic medicines that will permanently redefine the course of their conditions. Potential best in class progranulin raising FTD-GRN gene therapy program Established manufacturing and process analytics capabilities S
Slide 4: Pipeline with Potential to Address Multiple Neurodegenerative Diseases
4 Pipeline with Potential to Address Multiple Neurodegenerative Diseases Program Indication US/EU prevalence Discovery Pre-clinical 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
Slide 5: PBFT02 Has Demonstrated Best in Class Potential in FTD-GRN
5 • One time therapy • Durable, supraphysiologic CSF PGRN levels • Administration directly to CSF with nonsurgical injection Lead Clinical Program: PBFT02 Has Demonstrated Best in Class Potential in FTD-GRN Differentiated, Potential Best in Class Product Profile Initial Data from First 3 Treated Pat
Slide 6: Leading CMC Capabilities Via a Hybrid Approach
6 Discovery UPenn GTP Research Analytics and Vector Engineering Process/Analytic Development Passage CMC R&D Lab Proven Analytical Capabilities Integrated Process Development GMP QC Capabilities Strong Regulatory CMC Scientific Expertise Scale-up Capability GMP Manufacturing Longstanding Partnership
Slide 7: PBFT02 Frontotemporal Dementia — GRN
PBFT02 Frontotemporal Dementia — GRN
Slide 8: FTD-GRN: A Devastating Adult Disease
8 FTD-GRN: A Devastating Adult Disease 10pt Calibri footer 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 EPIDEMIOLOGY • Approximately 5–10% of all FTD is
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 Source: Rhinn H et al. Trends Pharm Sci. 2022, 43:641-652
Slide 10: PBFT02
10 PBFT02 • 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 biodistribution –Lower doses compared to I
Slide 11: PBFT02 Achieved Supraphysiologic Levels of CSF Progranulin in NHPs
11 Preclinical: PBFT02 Achieved Supraphysiologic Levels of CSF Progranulin in NHPs • AAV1 increased CSF PGRN levels ~5x more than AAV5 and AAVhu68 (proprietary AAV9 variant) vectors, without further elevating peripheral levels Left, right: Two adult rhesus macaques per treatment received ICM AAV.hPG
Slide 12: Supraphysiologic PGRN Increases Potential for Improved Cellular Function
12 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 mul
Slide 13: Higher CSF PGRN May Confer Reduction in Inflammatory Response
13 Preclinical: Higher CSF PGRN May Confer Reduction in Inflammatory Response Thalamus data shown above. Thalamic atrophy is a key feature commonly found in FTD PBFT02 reduced lipofuscin at all doses, suggesting correction of underlying mechanism of disease • Lipofuscin: increased levels associated
Slide 14: PBFT02 Showed Dose-Related Increases in CSF Progranulin in NHPs
14 Preclinical: PBFT02 Showed Dose-Related Increases in CSF Progranulin in NHPs Adult rhesus macaques received ICM PBFT02 (n = 3/dose) or vehicle (n =2) on study day 0. CSF was sampled 14 days post-dose. Human PGRN Levels in CSF of NHPs 14 days post-ICM Dose 0 2 4 6 8 10 12 High Dose Medium Dose Low
Slide 15: upliFT-D: Global Phase 1/2 Trial with PBFT02
15 upliFT-D: Global Phase 1/2 Trial with PBFT02 OPTIONAL DOSE 3 DOSE 2 (1.1e11 GC/g)* DOSE 1 (3.3e10 GC/g)* COHORT 1 COHORT 2 OPTIONAL COHORT 3 Trial Design Phase 1/2, multicenter, open-label, dose escalation study; up to 15 patients across 3 cohorts Duration 2 years; with additional 3 years of foll
Slide 16: upliFT-D: Interim Data from First Treated Patients
16 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 not experience SAEs; only mild-to-m
Slide 17: Following Protocol Update, Patients 2 & 3 had no SAEs
17 Following Protocol Update to Increase Steroids, Patients 2 & 3 had no SAEs or Evidence of Significant Immune Response Patient 1 Patient 2 Patient 3 Immunosuppression1 Day -1-60: 60 mg oral prednisone Days 1-3: 1,000 mg IV methylprednisolone Days 4-60: 60 mg oral prednisone LFTs Day 14-21 and Day
Slide 18: Initial Patients Have Seen a Substantial Increase in CSF PGRN
18 • Dose 1 resulted in supraphysiologic levels of CSF PGRN at Day 30 for all patients –Greater than 2-3x normal healthy adult levels at Day 30 following treatment (n=3) • Increase in CSF PGRN was sustained at 6- months (n=1) • Results exceeded what was observed in NHPs Shading: Reference range for
Slide 19: Plasma PGRN Levels Remained Below Normal Levels Post-Dose
19 Shading: Lower limit of normal of reference range for healthy adult controls’ PGRN levels in plasma (91.6 – 372.4 ng/mL, n = 56) (Passage Bio data) • 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 defi
Slide 20: Summary
20 Summary AEs=adverse events; ICM=intra-cisterna magna 1 Patient safety follow-up ranged from 2 to 8 months post-dosing as of data cutoff of Feb 14, 2024 *Reference range for normal, healthy adult controls’ PGRN levels in CSF (range: 3.28 – 8.15 ng/mL, mean: 4.76 ng/mL, n = 61) (Passage Bio data) S
Slide 21: Looking Ahead
Looking Ahead Passage Bio
Slide 22: PBFT02 Potential in FTD-GRN, FTD-C9orf72, and ALS
22 PBFT02 has Potential to Correct Underlying Pathology in FTD-GRN, FTD-C9orf72, and ALS Elevating PGRN in TDP-43 models results in: • Normalized cytoplasmic TDP-43 accumulation • Improved survival2 Supraphysiologic PGRN ameliorates TDP-43 pathology in preclinical models 1Rhinn H et al. Trends Pharm
Slide 23: PBFT02 has Potential to Modulate Alzheimer's Disease
23 PBFT02 has Potential to Modulate Alzheimer’s Disease • 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 Genetic risk1 SNP: single nucleotide polymorphism Third-party preclinical data. Source
Slide 24: Upcoming Milestones and Corporate Updates
24 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 25: Our Vision
25 Our Vision To improve patient lives with neurodegenerative diseases by delivering genetic medicines that will permanently redefine the course of their conditions. Potential best in class progranulin raising FTD-GRN gene therapy program Established manufacturing and process analytics capabilities
Slide 26: Thank You
Thank You passagebio.com | NASDAQ: PASG
Slide 27: Demonstrated Leadership
27 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
Slide 28: Intra-Cisterna Magna (ICM) Administration
28 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