Slide 1: PBGM01 Study in Infantile GM1 Gangliosidosis: Interim Clinical Results and Program Update
PBGM01 Study in Infantile GM1 Gangliosidosis Interim Clinical Results from Cohorts 1-4 and Program Update of Imagine-1 Clinical Study August 7, 2023
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 of, the Private Securities Litigation Reform Act of 1995, including, but not limited to: our expectations about timing and execution of anticipa
Slide 3: Executive Summary
3 Executive Summary Mark Forman, M.D., Ph.D.
Slide 4: Welcome & Agenda
4 Welcome & Agenda Welcome Will Chou, M.D. Executive Summary Mark Forman, M.D., Ph.D. Imagine-1 Interim Clinical Results and Program Update Samiah Al-Zaidy, M.D. Closing Remarks Will Chou, M.D. Q&A Will Chou, M.D. Chief Executive Officer, Passage Bio Mark Forman, M.D., Ph.D. Chief Medical Officer, P
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 approved
Slide 6: GM1 Gangliosidosis Disease Continuum
6 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 • Skel
Slide 7: Key Objectives for Imagine-1 Study
7 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 8: Promising Interim Data from First Treated Patients
8 Promising Interim Data from First 8 Treated Patients Favorable safety profile and well-tolerated Initial evidence of improved survival in study participants Dose-dependent increase in CSF β-Gal activity, with increase sustained up to 12-months post-dose Dose-dependent decrease in β-Gal substrate (
Slide 9: Imagine-1 Interim Clinical Results
9 Imagine-1 Interim Clinical Results Samiah Al-Zaidy, M.D.
Slide 10: Imagine-1: Global Phase 1/2 Trial with PBGM01
10 Imagine-1: Global Phase 1/2 Trial with PBGM01 COHORT 4 Early Infantile n = 2 DOSE 2 (1.1e11 GC/g)* DOSE 1 (3.3e10 GC/g)* COHORT 2 Late Infantile n = 2 COHORT 3 Early Infantile n = 2 COHORT 1 Late Infantile n = 2 60 days between subject enrollment IDMC review Dosing complete * Genome copies per gr
Slide 11: Imagine-1 Baseline Patient Characteristics
11 Imagine-1 Baseline Patient Characteristics 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 Dose level received Dose 1 Dose 1 Dose 1 Dose 2 Dose 1 Dose 2 Dose 2 Dos
Slide 12: Imagine-1 Study: Cohorts 1-4 Safety & Tolerability
12 Imagine-1 Study: Cohorts 1-4 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 measured by
Slide 13: Initial Evidence of Improved Survival vs. Natural History
13 Initial Evidence of Improved Survival Among Study Participants vs. Natural History * From Lang FM, et al. Mol Genet Metab. 2020;129(3):228-235. Lang et al meta-analysis defined GM1 Type I as disease onset <12 months of age (n=154) 0.0 0.2 0.4 0.6 0.8 1.0 0 10 20 30 40 50 60 Probability of Overall
Slide 14: Dose 1 Exhibited Modest Effects on Key CSF Biomarkers
14 Dose 1 Exhibited Modest Effects on Key CSF Biomarkers 0 500 1,000 1,500 2,000 2,500 3,000 3,500 4,000 0 30 60 90 120 150 180 210 240 270 300 330 360 390 420 450 Gangliosides, apparent nM Time (days) Dose 1 GM1 Ganglioside, CSF P1 Late Infantile P2 Late Infantile P3 Early Infantile P5 Early Infant
Slide 15: Dose 2 Resulted in Robust Increases in CSF β-Gal Activity
15 Dose 2 Resulted in Robust Increases in CSF b-Gal Activity and Decreases in GM1 Gangliosides 0 200 400 600 0 30 60 90 120 150 180 210 240 270 300 330 360 Gangliosides, apparent nM Time (days) Dose 2 GM1 Ganglioside, CSF P4 Late Infantile P6 Late Infantile P7 Early Infantile P8 Early Infantile β-Ga
Slide 16: Summary
16 Summary AEs=adverse events; ICM=intra-cisterna magna *Based on preliminary data from University of Pennsylvania’s ODC Natural History Study (NHS) (NCT04041102). SAFETY & CLINICAL DATA PBGM01 continues to have a favorable safety profile in both early and late infantile GM1 • No serious AEs related
Slide 17: Program Update
17 Program Update Samiah Al-Zaidy, M.D.
Slide 18: Preclinical Rationale for Dose Escalation
18 Preclinical Rationale for Dose Escalation • Expectation of further increase in b-Gal activity and improved lysosomal function • Dose 3 (2.2 x 1011 GC/g) maintains safety window to maximum dose tested in NHP toxicology study Advancing Program to Evaluate Higher Dose (Dose 3) Potential for an incre
Slide 19: PBGM01 – Amended Protocol
19 PBGM01 – Amended Protocol Addition of 2 cohorts to explore dose 2x higher than Dose 2 • Concurrent dosing of Early and Late Infantile GM1 • Updated Inclusion/Exclusion Criteria to enroll children with earlier stage of disease Early Infantile: − Decreased age at enrollment from 4-24 months to 1-12
Slide 20: Closing Remarks
20 Closing Remarks Will Chou, M.D.
Slide 21: Imagine-1 Progressing Well Against Key Study Objectives
21 Imagine-1 Progressing Well Against Key Study Objectives Establish Safety Profile of PBGM01 Determine Optimal Dose for Therapeutic Effect Understand PBGM01 Benefit Across Infantile GM1 Patient Populations ✓ Favorable safety and immunological profile at Dose 1 & 2 − No SAEs related to study treatme
Slide 22: PBGM01 Program Anticipated Next Steps
22 PBGM01 Program Anticipated Next Steps • Treated first patient at Dose 3 in July • Plan to share initial safety and biomarker data from Dose 3 by mid-2024 Complete enrollment of Cohorts 5 and 6 • Analyze data from Cohorts 1-6 to establish safety/tolerability profile and therapeutic potential of ea
Slide 23: Passage Bio
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