Passage Bio, Inc. · NASDAQ:PASG
Passage Bio — AD/PD 2025 International Conference
14 slides from Passage Bio's conference presentation, Apr 3, 2025
Slide 1: Interim Safety and Biomarker Data from upliFT-D Trial of PBFT02 in FTD with GRN Mutation
Interim Safety and Biomarker Data from upliFT-D Trial of PBFT02 in FTD with GRN Mutation Forman MS, Voss T, Triglia P, Ni YG, Browne SE, Quadrini KJ, Chou W, Ducharme S, Irwin DJ, Santana I, Schulz PE, Takada L, Tartaglia C, de Souza LC ADPD 2025 #2589
Slide 2: Disclosures
Disclosures • upliFT-D trial is also known as PBFT02-001, NCT04747431 • Sue Browne, PhD: 2
Slide 3: Frontotemporal Dementia: A Devastating Disease Syndrome
Frontotemporal Dementia: A Devastating Disease Syndrome • FTD is a common cause of early-onset dementia accounting for 20% of cases, second only to AD FTD-GRN • Signs and symptoms typically manifest in • 5 to 10% of FTD is caused by adulthood, and are often misdiagnosed initially: mutations in granu
Slide 4: Progranulin (PGRN) Deficiency is the Defining Characteristic of FTD-GRN, Leading to Neurodegeneration
Progranulin (PGRN) Deficiency is the Defining Characteristic of FTD-GRN, Leading to Neurodegeneration Progranulin is critical to maintaining CNS cell homeostasis Decreased PGRN Neuronal dysfunction, pathological Neuronal vulnerability Neurodegeneration changes and inflammation in affected regions Ou
Slide 5: AAV1 Selected as Vector after Capsid Comparison in NHPs. Robust Vector Delivery to Brain
AAV1 Selected as Vector after Capsid Comparison in NHPs. Robust Vector Delivery to Brain Regions affected in FTD Superior hPGRN levels in NHP CSF after ICM AAV1 ICM PBFT02 administration to NHPs resulted in compared to AAV5 and AAVhu68 (AAV9 variant) high gene distribution throughout the CNS AAV1.CB
Slide 6: upliFT-D: Global Phase 1/2 Trial with PBFT02
upliFT-D: Global Phase 1/2 Trial with PBFT02 DURATION 2 years. Additional 3 years follow-up for safety and durability of effect TRIAL DESIGN PRIMARY ENDPOINTS Safety and tolerability 1/2 Biomarkers Phase Multicenter Open-label Dose exploration • Progranulin (CSF, plasma) FTD-GRN • NfL (CSF, plasma)
Slide 7: Key Eligibility and Baseline Demographics for UpliFT-D FTD-GRN Dose 1 Participants
Key Eligibility and Baseline Demographics for UpliFT-D FTD-GRN Dose 1 Participants DOSE 1 (n=7) Mean / % / n Range Eligibility Age (yrs) 63.3 51-71 • Ages 35 to 75, inclusive Sex M: 57% F: 43% • Pathogenic GRN mutation carrier bvFTD: 5 FTD-GRN phenotype (n) lvPPA: 1 • Symptomatic FTD-GRN svPPA: 1 Di
Slide 8: upliFT-D: Interim Safety Profile
upliFT-D: Interim Safety Profile Interim Safety Highlights* - Dose 1 PBFT02 in FTD-GRN Patients (n=7) • In 5 of 7 participants, all treatment emergent AEs were mild to moderate • 2 of 7 participants experienced a total of 3 SAEs – Participant 1: asymptomatic venous sinus thrombosis (VST) and hepatot
Slide 9: PBFT02 Dose 1 Associated with Expected Immune Responses to Capsid. No Response to hPGRN
PBFT02 Dose 1 Associated with Expected Immune Responses to Capsid. No Response to hPGRN Detected Anti-AAV1 Neutralizing Antibody Responses in CSF • No Dose 1 participant had anti-AAV1 neutralizing antibodies at baseline • As expected, most participants developed anti-AAV1 antibodies in CSF and serum
Slide 10: PBFT02 Generated Robust, Durable Increases in CSF PGRN
PBFT02 Generated Robust, Durable Increases in CSF PGRN Progranulin in CSF is elevated after Dose 1 PBFT02 Promising PGRN profile: 40 • Consistent elevation from baseline • Durable to 18 months 30 • Levels overall plateauing by 6-12 PGRN, ng/mL months 20 CSF Progranulin (ng/mL) in FTD-GRN Participant
Slide 11: PGRN Elevation Localized to CNS Following ICM PBFT02 Administration
PGRN Elevation Localized to CNS Following ICM PBFT02 Administration Plasma PGRN below healthy adult levels after Dose 1 PBFT02 150 • Plasma PGRN levels remained below normal levels up to 12 months post-dose Healthy adult range in FTD-GRN patients PGRN, ng/mL 100 • PGRN increased only in the CNS, whe
Slide 12: Plasma NfL Showed Early Evidence of Improvement in a Disease Progression Biomarker vs Natural History
Plasma NfL Showed Early Evidence of Improvement in a Disease Progression Biomarker vs Natural History • Plasma NfL is the only FTD-GRN disease progression biomarker with published natural history data1,2 • Both participants 12 M post-PBFT02 had a reduced annual rate of change in plasma NfL compared
Slide 13: Conclusions: PBFT02 Dose 1 in FTD-GRN
Conclusions: PBFT02 Dose 1 in FTD-GRN • Dose 1 PBFT02 demonstrated robust, consistent elevation of CSF PGRN and was durable up to 18 months post-treatment • Early evidence of improvement in disease progression vs. natural history as measured by plasma NfL • PBFT02 was well tolerated in 5 of 7 Dose 1
Slide 14: We would like to thank the patients, families, caregivers, investigators, and our collaborators
We would like to thank the patients, families, caregivers, investigators, and our collaborators