Slide 1: PBGM01 Study in Infantile GM1 Gangliosidosis: Interim Clinical Results from Cohorts 1-3
PBGM01 Study in Infantile GM1 Gangliosidosis Interim Clinical Results from Cohorts 1 - 3 of Imagine - 1 Clinical Study December 14, 2022
Slide 2: Forward-Looking Statements
2 Forward - Looking Statements This presentation includes “forward - looking statements” within the meaning of, and made pursuant to the safe harbor provisions o f, the Private Securities Litigation Reform Act of 1995, including, but not limited to: our expectations about timing and execution of ant
Slide 3: Welcome & Agenda
3 Welcome & Agenda Executive Summary Will Chou, M.D. Overview of GM1 Gangliosidosis Jeanine Jarnes, PharmD, BCOP, BCPS Review of Safety, Biomarker, and Preliminary Efficacy Results Mark Forman, M.D., Ph.D. Closing Remarks Will Chou, M.D. Q&A Will Chou, M.D. Chief Executive Officer, Passage Bio Mark
Slide 4: Executive Summary
4 Executive Summary Will Chou, M.D.
Slide 5: PBGM01 is a Potentially Transformative Therapy for GM1 Gangliosidosis
5 PBGM01 is a Potentially Transformative Therapy for GM1 Gangliosidosis, a Rare, Underserved Disorder GM1 GANGLIOSIDOSIS • Inherited lysosomal storage disease that leads to progressive damage to both the CNS and peripheral tissues • Caused by loss - of - function mutations in the GLB1 gene • No appr
Slide 6: Interim Data from First Treated Patients Positions PBGM01 as Promising Option
6 Interim Data from First 6 Treated Patients Positions PBGM01 as a Promising Potential Treatment Option for GM1 AEs=adverse events; ICM=intra - cisterna magna. SAFETY Favorable safety profile and well - tolerated • No serious AEs related to study treatment • No evidence of DRG toxicity • No evidence
Slide 7: Overview of GM1 Gangliosidosis
7 Overview of GM1 Gangliosidosis Jeanine Jarnes, PharmD, BCOP, BCPS
Slide 8: GM1 Gangliosidosis: A Devastating Pediatric Disease
8 GM1 Gangliosidosis: A Devastating Pediatric Disease FATAL, PEDIATRIC NEUROLOGICAL LYSOSOMAL STORAGE DISORDER caused by GLB1 gene mutations characterized by destruction of neurons in the brain and spinal cord. Characterized by rapidly progressive neurological decline resulting in reduced muscle ton
Slide 9: GM1 Gangliosidosis Disease Continuum
9 GM1 Gangliosidosis Disease Continuum GM1 Gangliosidosis is a Continuum Disease Severity Residual Enzyme Activity (Serum) Focus of Imagine - 1 Trial Negligible to 5% ~ 1 – 5% ~ 3 – 10% Type 1 (Early Infantile) • Onset <6 months • Hypotonia • Neurodegeneration • Developmental regression • Seizures •
Slide 10: Natural History of Infantile GM1
10 Onset before 6 months of age Rapid disease progression with no new developmental milestones reached after 3 - 6 months Survival: <2 years Early Infantile (Type I) Onset between 6 months to 2 years of age Relatively s lower disease progression with no new developmental milestones reached after 12
Slide 11: Rapid Decline in Infantile GM1 with <20% Survival at Months
11 Rapid Decline in Infantile GM1 with <20% Survival at 24 Months 1 1. Lang FM et al., Mol Genet Metab.2020;129:228 - 235 • S ymptom onset: 2.8 months • F irst admission: 6.3 months • D iagnosis: 8.7 months • D eath: 18.9 months Mean age of: Cumulative time - to - event analysis of key points during
Slide 12: Review of Safety, Biomarker, and Preliminary Efficacy Results in Cohorts 1-3
12 Review of Safety, Biomarker, and Preliminary Efficacy Results in Cohorts 1 - 3 Mark Forman, M.D., Ph.D.
Slide 13: Imagine-1: Global Phase 1/2 Trial with PBGM01
13 Imagine - 1: Global Phase 1/2 Trial with PBGM01 Completed dosing of all patients in dose - ascending portion of study COHORT 4 Early Infantile D OSE 2 (1.1e11 GC/g)* D O S E 1 (3.3e10 GC /g)* Expansion Cohort Early Infantile Expansion Cohort Late Infantile COHORT 2 Late Infantile COHORT 3 Early I
Slide 14: Imagine-1 Baseline Patient Characteristics
14 Imagine - 1 Baseline Patient Characteristics Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Diagnosis Late Onset Late Onset Early Onset Late Onset Early Onset Late Onset Dose level received Low dose Low dose Low dose High dose Low dose High dose Cohort 1 1 3 2 3 2 Gender Male Male Fe
Slide 15: Imagine-1 Study Cohorts: Safety & Tolerability
15 Imagine - 1 Study: Cohorts 1 - 3 Safety & Tolerability No treatment - related serious adverse events (SAEs) All treatment - related adverse events (AEs) were mild - to - moderate in severity No clinically significant changes in liver function requiring intervention No evidence of DRG toxicity, as
Slide 16: Favorable Immunological Profile At Interim Analysis
16 Favorable Immunological Profile At Interim Analysis Observations following ICM administration of PBGM01: Neutralizing antibodies to capsid detected at low levels in CSF after Day 30; not expected to affect CNS gene transfer As anticipated, moderate serum neutralizing antibodies developed to capsi
Slide 17: PBGM01 ICM Delivery Resulted in Increased Transgene Activity in CSF
17 0 1 2 3 4 5 6 0 60 120 180 240 300 360 β - Gal, nmol/mL/3hr Time (days) β - gal, CSF P1 Late Infantile P2 Late Infantile P3 Early Infantile P5 Early Infantile NHS patient value range PBGM01 ICM Delivery Resulted in Increased Transgene Activity in CSF 0 1 2 3 4 5 6 0 60 120 180 240 300 360 β - Gal
Slide 18: High Dose PBGM01 Led to Decreases in CSF GM1 Gangliosides
18 High Dose PBGM01 Led to Decreases in CSF GM1 Gangliosides 0 200 400 600 0 50 100 150 200 250 300 350 Gangliosides, apparent nM Time (days) GM1 Ganglioside, CSF P4 Late Infantile P6 Late Infantile 0 200 400 600 800 1,000 0 50 100 150 200 250 300 350 Gangliosides, apparent nM Time (days) GM1 Gangli
Slide 19: Patients Manifest a Wide Range of Developmental Delay at Baseline
19 Patients Manifest a Wide Range of Developmental Delay at Baseline Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Diagnosis Late Onset Late Onset Early Onset Late Onset Early Onset Late Onset Dosing Cohort Low dose Low dose Low dose High dose Low dose High dose Chronological age at ba
Slide 20: Milder Developmental Delay at Dosing Associated with Improved Treatment Response
20 Preliminary Trend: Milder Developmental Delay at Dosing Associated with Improved Treatment Response 10pt Calibri footer *The Vineland - II is caretaker - assessed. **The Bayley - III is based on direct observation by a neurodevelopmental specialist. 0 5 10 15 20 25 6 8 10 12 14 16 18 20 22 24 26
Slide 21: Summary
21 Summary AEs=adverse events; ICM=intra - cisterna magna. SAFETY Favorable safety profile and well - tolerated • No serious AEs related to study treatment • No evidence of DRG toxicity • No evidence of cell - mediated immune response • No complications related to ICM injection BIOMARKERS • High dos
Slide 22: Closing Remarks
22 Closing Remarks Will Chou, M.D.
Slide 23: Key Objectives for Imagine-1 Study
23 Key Objectives for Imagine - 1 Study Establish Safety Profile of PBGM01 Determine Optimal Dose for Therapeutic Effect Understand PBGM01 Benefit Across Infantile GM1 Patient Populations
Slide 24: Data from Cohort 4 Will Add to Understanding of Dose and Patient Selection
24 Data from Cohort 4 Will Add to Understanding of Dose and Patient Selection Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Patient 7 Patient 8 Diagnosis Late Onset Late Onset Early Onset Late Onset Early Onset Late Onset Early Onset Early Onset Dosing Cohort Low dose Low dose Low dose
Slide 25: PBGM01 Program Anticipated Next Steps
25 PBGM01 Program Anticipated Next Steps • Present additional data from Cohorts 1 - 3 at 19th Annual WORLD Symposium in February 2023 • Present initial data from Cohort 4 (early infantile, high dose) by mid - 2023 Share additional data throughout 2023 • Analyze data from Cohort 4 • Due to observed d
Slide 26: Passage Bio
Passage Bio ieare nc eaggDR Ieee