Passage Bio, Inc. · NASDAQ:PASG
Passage Bio — Investor Presentation (September 2020)
39 slides from Passage Bio's investor presentation, Sep 9, 2020
Slide 1: Corporate Presentation September 2020
Corporate Presentation SEPTEMBER 2020
Slide 2: Forward-Looking Statements
Forward - Looking Statements 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 expectation about timing and execution of antic
Slide 3: Passage Bio Company Overview
Passage Bio Company Overview 3 Establishing dedicated manufacturing capabilities Deep pipeline of potentially transformative genetic medicines Collaboration with UPenn’s Gene Therapy Program and Orphan Disease Center Multiple potential value creating clinical catalysts Cash runway into 2023 Differen
Slide 4: Board of Directors and Leadership Team
4 BOARD OF DIRECTORS Tachi Yamada, M.D. (Chair) Frazier Patrick Heron Frazier Stephen Squinto , Ph.D. OrbiMed Tom Woiwode , Ph.D. Versant Sandip Kapadia Intercept Saqib Islam, J.D. SpringWorks Liam Ratcliffe , M.D., Ph.D. Access Industries Athena Countouriotis , M.D. Turning Point Bruce Goldsmith, P
Slide 5: The Passage Bio Approach
The Passage Bio Approach Differentiated to achieve a higher probability of technical and regulatory success 5 M itigation of early developmental risk of programs prior to IND submission M itigation of clinical development risk through our relationships with the Orphan Disease Center (ODC) at Penn St
Slide 6: Deep Portfolio of Candidates in Rare Monogenic CNS Disorders
Program Indication Gene Discovery Candidate selection IND - enabling Phase 1/2 Pivotal Milestones Global commercial rights PB GM01 1 GM1 GLB1 • Initiate Phase 1/2 clinical trial in 4q 2020 1q 2021 PB FT02 FTD GRN • Initiate Phase 1/2 clinical trial in 1h 2021 PB KR03 Krabbe GALC • Initiate Phase 1/2
Slide 7: Our Programs
Our Programs d Passage
Slide 8: GM1: Infantile GM1 Gangliosidosis, PBGM01
GM1: Infantile GM1 Gangliosidosis PBGM01 a potential transformative therapy for a rare, underserved disorder 8 Source: NIH, CHOP, American Journal of Neuroradiology Severe lysosomal storage disease • Spectrum of disease caused by GLB1 gene mutations • Symptoms include reduced muscle tone, progressiv
Slide 9: PBGM01: Knock Out Mouse Model Biomarker and Pathophysiology Data
PBGM01: Knock Out Mouse Model Clear, supportive preclinical biomarker and pathophysiology data Increased Biomarker Activity • Stable, dose - dependent increases in β - gal expression in the brain and peripheral organs • Increased β - gal enzyme activity in serum, brain, cerebrospinal fluid and criti
Slide 10: PBGM01: Knock Out Mouse Model Functional Data
PBGM01: Knock Out Mouse Model Clear, supportive preclinical functional data Preservation of Neurological Function Dose related improvements in neurological function demonstrated Top two doses similar to GLB +/ - vehicle 0 5 10 15 20 Total score ( + SEM) Days 240 180 120 60 0 Neurological Examination
Slide 11: PBGM01: Phase 1/2 Clinical Trial Update
PBGM01: Phase 1/2 Clinical Trial Update 11 Submitted IND to FDA for proposed Phase 1/2 dose - escalating trial in June 2020 Received FDA clinical hold letter confirming that IND has been placed on clinical hold due solely to the biocompatibility of the proposed ICM delivery device Discussions ongoin
Slide 12: PBGM01: Phase 1/2 Trial
PBGM01: Phase 1/2 Trial First patient enrollment expected in late 4q20 or early 1q21 12 Trial design Phase 1/2, multi - center, open - label, single - arm, 2+2 dose escalation and confirmatory study of PBGM01 in two separate cohorts of pediatric subjects with Late Onset Infantile GM1 and Early Onset
Slide 13: FTD-GRN: Frontotemporal Dementia Caused by a Progranulin Deficiency
FTD - GRN: Frontotemporal Dementia Caused by a Progranulin Deficiency A potential transformative therapy for a rare, underserved disorder 13 Devasting form of dementia FTD is one of the more common causes of early - onset dementia Approximately 5 - 10% of FTD is caused by a GRN gene mutation, causin
Slide 14: FTD-GRN: Capsid Comparison Study in NHPs
FTD - GRN: Capsid Comparison Study in NHPs AAV1 Capsid significantly increases PRGN in CSF over normal levels 14 ▪ AAV1 capsid provides strong transduction of ependymal cells compared to other vectors (e.g., AAVhu68) ▪ AAV1 Capsid differentially increased CSF Levels 50 fold higher than normal human
Slide 15: FTD-GRN: Knock out Mouse Model Comparing Lipofuscin Deposits
Hippocampus Thalamus 0 200 400 600 800 WT KO+PBS KO+AAV Lipofuscin Count Cortex 0 20 40 60 80 100 WT KO+PBS KO+AAV Lipofuscin Count p<0.05, p<0.001, p<0.0001 FTD - GRN: Knock out Mouse Model Comparing Lipofuscin Deposits Preclinical data supporting underlying pathophysiology of FTD - GRN 0 20 40 60
Slide 16: PBFT02: Clinical Development
PBFT02: Clinical Development Trial initiation expected in 1h21 16 TRIAL DESIGN A Phase 1/2, Multi - Center, Open Label, Single - arm, Dose Escalation Study to Assess the Safety and Tolerability of a Single Dose of PBFT02 Delivered into the Cisterna Magna (ICM) of Adult Subjects with Frontotemporal D
Slide 17: Krabbe: Lysosomal Storage Disease, PBKR03
Krabbe : Lysosomal Storage Disease PBKR03 a potential transformative therapy for a rare, underserved disorder 17 Source: NIH, CHOP, American Journal of Neuroradiology Severe Form of Disease Infantile Krabbe disease is the most severe form, accounting for 60% to 70% of diagnoses Disease progression i
Slide 18: PBKR03: Disease Model Data Twitcher Mouse and Dog Models
PBKR03: Disease Model Data Twitcher Mouse and Dog Models Clear, supportive preclinical predictive, functional and pathophysiology data Increased biomarker activity Increased GALC activity in brain, liver and serum in naturally occurring twitcher mouse Also increased GALC activity in the CSF in natur
Slide 19: PBKR03: Naturally Occurring Dog Model
PBKR03: Naturally Occurring Dog Model Clear, supportive preclinical data 19 Naturally occurring Krabbe Dog model study Treatment Animals treated using ICM at 3 weeks, which approximates treatment timing in humans 2 sham treated animals; 4 PBKR03 - treated animals; 1 sham treated wildtype control Unt
Slide 20: PBKR03: Clinical Development
PBKR03: Clinical Development Trial initiation expected in 1h21 20 TRIAL DESIGN Phase 1/2, FIH, multi - center , open - label, single - arm, dose escalation study of PBKR03 administered by a single ICM injection in pediatric subjects with infantile Krabbe disease INTERVENTION Single ICM dose of AAVhu
Slide 21: Financial Summary
Financial Summary 21 ▪ Strong cash balance of $353M at June 30, 2020 ▪ Cash on hand to fund operations into 2023 ▪ Runway to potentially deliver multiple meaningful catalysts over multiple programs
Slide 22: Anticipated Upcoming Milestones
Anticipated Upcoming Milestones 22 ▪ Initiate Phase 1/2 trial for PBGM01 in patients with infantile GM1 late in 4q20 or early 1q21 ▪ Initiate Phase 1/2 trials for PBFT02 in FTD and PBKR03 in Krabbe disease in 1h21 ▪ Advance PBML04, PBLA05 and PBCM06 toward IND - enabling studies ▪ Continue to evalua
Slide 23: Appendix
W PassageBio Appendix
Slide 24: Strategic Manufacturing Collaboration Established
Strategic Manufacturing Collaboration Established Programs will utilize a Passage Bio dedicated cGMP facility 24 Manufacturing Technology Mammalian cells rAAV platform Transient transfection Single - use fixed - bed iCellis ® manufacturing platform First - in - human (FIH) process and analytical dev
Slide 25: GM1
GM1 d Passage Bio
Slide 26: Preclinical Data Showed an Increase in β-gal Activity in GLB1 Knockout Mice
Preclinical Data Showed an Increase in β - gal Activity in GLB1 Knockout Mice Treated with PBGM01 26 We believe PBGM01 has the potential to increase levels of β - gal activity in the brain, cerebrospinal fluid (CSF) and critical peripheral tissues GLB1 +/ - + PBS GLB1 - / - + PBS GLB1 - / - + AAV 10
Slide 27: Neurological Examination Showed Dose-Related Preservation of Function in Mice
Neurological Examination Showed Dose - Related Preservation of Function in Mice Treated with PBGM01 27 Improvements in both internal biology and external measures of neurological function further support PBGM01’s potential to reverse developmental regression and prevent further central and periphera
Slide 28: Histological Analysis Demonstrated Dose-Related Reduction in Brain Storage Lesions
Histological Analysis Demonstrated a Dose - Related Reduction in Brain Storage Lesions Automated quantification of LAMP1+ cells in entire cortex of one coronal brain section. One - way ANOVA of log - transformed data followed by Dunnett’s test GLB1 +/ - + vehicle GLB1 - / - + vehicle GLB1 - / - + PB
Slide 29: PBGM01: Knock Out Mouse Model Survival Data
PBGM01: Knock Out Mouse Model Clear, Supportive Preclinical Survival Data Survival PBGM01 Dose - Related Effect on Survivability p<0.0001, p=0.0002, each as compared to KO + Vehicle. GLB1 - / - (KO) GLB1 +/ - (HET) Dose 4 (highest) Dose 3 Dose 2 Dose 1 (lowest) Vehicle Vehicle Percent Survival 0 Day
Slide 30: FTD
FTD d Passage Bio
Slide 31: Histology Comparison of Lipofuscin Deposits in the Brain
Histology Comparison of Lipofuscin Deposits in the Brain AAV - treated GRN - / - mice exhibited fewer lipofuscin deposits in all brain regions compared to those of vehicle - treated GRN - / - mice Hippocampus Thalamus 0 200 400 600 800 WT KO+PBS KO+AAV Lipofuscin Count Cortex 0 20 40 60 80 100 WT KO
Slide 32: Capsid Comparison Study in NHPs Using an AAV1 Capsid
Capsid Comparison Study in NHPs Demonstrated That Using an AAV1 Capsid Differentially Increased CSF Levels of Progranulin Without Further Elevating Plasma Levels 32 We believe PBFT02 has the potential to increase PGRN levels in the brain sufficiently to overcome the intracellular deficiency of progr
Slide 33: PBFT02 Utilizes an AAV1 Capsid With Strong Transduction of Ependymal Cells
PBFT02 Utilizes an AAV1 Capsid Which Provides Strong Transduction of Ependymal Cells 33 We believe PBFT02 has the potential to be a transformative therapy for patients suffering from FTD - GRN given its superior transduction of ependymal cells in the brain which differentially increases CSF progranu
Slide 34: Proactive Exploration of AAV-Related DRG Toxicity
Proactive Exploration of AAV - Related DRG Toxicity DRG toxicity was previously identified as potential AAV platform risk DRG toxicity has been seen across capsids, transgenes and delivery methods NHP studies where minimal to mild dose - dependent DRG toxicity was observed without clinical manifesta
Slide 35: Krabbe
Krabbe d Passage Bio
Slide 36: PBKR03 Increased Brain and Peripheral Organ GALC Activity
PBKR03 Treatment Showed an Increase in Brain and Peripheral Organ GALC Activity in Naturally Occurring Twitcher Mouse Disease Model and Dog Disease Model 36 We believe PBKR03 has the potential to increase levels of GALC activity in the brain, CSF and critical peripheral tissues CSF GALC activity in
Slide 37: Dog Model Showed Normalization in Body Weight and Nerve Conduction Velocity
Further Studies in a Dog Model Showed a Normalization in Body Weight and Nerve Conduction Velocity 37 Treated dogs responded well to the therapy, showed similar growth and NCVs as wild - type dogs 0 20 40 60 80 6 weeks 12 weeks 20 weeks 28 weeks 42 weeks m/s K933-Krabbe AAV K937-Krabbe AAV K938-Krab
Slide 38: Histological Analysis Showed Improvement in Myelination and Decrease in Neuroinflammation
Histological Analysis Showed an Improvement in Myelination in Brain and Decrease in Neuroinflammation Histology: Myelination and Neuroinflammation Correction at 28 Weeks A Luxol blue (myelination) treated 28 weeks treated 28 weeks B IBA1 (neuroinflammation) sham 8 weeks sham 8 weeks ▪ Treated dogs d
Slide 39: Corporate Presentation SEPTEMBER 2020
Corporate Presentation SEPTEMBER 2020