Passage Bio, Inc. · NASDAQ:PASG
Passage Bio — Corporate Update (November 2023)
29 slides from Passage Bio's corporate update, Nov 13, 2023
Slide 1: Fulfilling the Promise of Genetic Medicine for Central Nervous System Disorders
Nasdaq: PASG © 2023 Passage Bio. All rights reserved. Fulfilling the Promise of Genetic Medicine for Central Nervous System Disorders November 2023
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 expectation about timing and execution of anticipate
Slide 3: Our Vision
3 Our Vision To fulfill the promise of genetic medicine by developing transformative therapies for people with devastating CNS diseases Two exciting lead gene therapy programs in FTD and GM1 Innovative research partnership with Penn’s Gene Therapy Program Established manufacturing and process analyt
Slide 4: Advancing Two Lead Clinical Programs
4 Global upliFT-D Dose-Escalation Study of PBFT02 NEXT MILESTONES Initial safety and biomarker data from three Cohort 1 patients in Q4 2023 Advancing Two Lead Clinical Programs FRONTOTEMPORAL DEMENTIA (FTD) A Detrimental Adult CNS Disease WHERE WE ARE Encouraging data emerging from first treated pat
Slide 5: Promising Preclinical Pipeline in Adult CNS Disorders
5 • Drug Candidate: PBAL05 • Gene Target: C9orf72 • Approach: miRNA and cDNA combination • Hexanucleotide repeat expansion in C9orf72 gene is found in 40% of familial and 8% of sporadic ALS cases1 • ~4,500 ALS-C9orf72 cases worldwide in 20202 AMYOTROPHIC LATERAL SCLEROSIS (ALS) • Drug Candidate: Unn
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 DEVASTATING FORM OF DEMENTIA caused by a GRN gene mutation resulting in progranulin (PGRN) deficiency and haploinsufficiency. Approximately 5–10% of FTD is caused by a GRN mutation. Disease progression is rapid and degenerative including loss of speech, loss of
Slide 9: Progranulin Deficiency Contributes to Neurodegeneration
9 Maintains lysosomal activity Progranulin Deficiency Contributes to Neurodegeneration Healthy Brain FTD Brain Reduced progranulin leads to neuronal dysfunction and death Progranulin is critical to maintaining CNS cell homeostasis Regulates microglial activation Regulates synapse number and structur
Slide 10: PBFT02 Our Approach
10 PBFT02 OUR APPROACH Proprietary construct delivers functional GRN gene encoding progranulin (PGRN) with potential therapeutic benefit of a one-time gene therapy approach PRECLINICAL EVIDENCE Compelling preclinical evidence from NHP studies • Broad transduction across the brain, including high tra
Slide 11: Intra-Cisterna Magna (ICM) Administration
11 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
Slide 12: PBFT02: NHP Preclinical Studies Utilizing ICM
12 PBFT02: NHP Preclinical Studies Utilizing ICM • PBFT02 achieved supraphysiologic levels of CSF PGRN in NHPs • AAV1 increased CSF PGRN levels ~5x more than AAV5 and AAVhu68 vectors, without further elevating peripheral levels 1. Hinderer et al., Annals Clin Trans Neurology. 2020 Left: Adult rhesus
Slide 13: PBFT02: Higher CSF PGRN May Confer Incremental Benefits
13 PBFT02: Higher CSF PGRN May Confer Incremental Benefits Microgliosis reduction strongest at highest doses / PGRN levels (murine FTD model) • Microgliosis: inflammatory response to pathogenic insults in the CNS • CD68: marker of activated microglia Thalamus data shown above. Thalamic atrophy is a
Slide 14: upliFT-D: Global Phase 1/2 Trial with PBFT02
14 upliFT-D: Global Phase 1/2 Trial with PBFT02 OPTIONAL DOSE 3 DOSE 2 (1.1e11 GC/g)* DOSE 1 (3.3e10 GC/g)* 60 days between subject enrollment COHORT 1 n = 3 COHORT 2 n = 3 OPTIONAL COHORT 3 n = 3 Trial Design Phase 1/2, multicenter, open-label, dose escalation study Route of Administration Intra-ci
Slide 15: GM1 Gangliosidosis
PBGMOlI1 ) PassageBio Life-transforming therapies GM1 Gangliosidosis
Slide 16: GM1 Gangliosidosis: A Devastating Pediatric Disease
16 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 to
Slide 17: GM1 Gangliosidosis Disease Continuum
17 GM1 Gangliosidosis Disease Continuum Disease severity inversely related to residual b-Gal enzyme activity Brunetti-Pierri N., Scaglia F. Mol Genet Metab. 2008;94(4):391-396. Jarnes JR, et al. Mol Genet Metab. 2017;121(2):170-179. Lang FM, et al. Mol Genet Metab. 2020;129(3):228- 235. Regier DS, T
Slide 18: PBGM01 Our Approach
18 PBGM01 OUR APPROACH Next-generation, proprietary capsid delivers functional GLB1 gene encoding β-Gal to the brain and peripheral tissues PRECLINICAL EVIDENCE Compelling preclinical data in knock-out mouse model • Dose-related histological correction, improvements in neurological function, and sur
Slide 19: Imagine-1: Global Phase 1/2 Trial with PBGM01
19 Imagine-1: Global Phase 1/2 Trial with PBGM01 Actively recruiting additional patients for Cohorts 5 & 6 Trial Design Phase 1/2, multi-center, open-label, dose escalation and confirmatory study Route of Administration Intra-cisterna magna (ICM) Capsid AAVhu68 Duration Two years, with rollover into
Slide 20: Key Takeaways from Cohorts 1-4 Interim Data
20 * Interim data as presented on August 7, 2023. 1Based on preliminary data from University of Pennsylvania’s ODC Natural History Study (NHS) (NCT04041102).. AEs=adverse events; ICM=intra-cisterna magna. Key Takeaways from Cohorts 1-4 Interim Data* SAFETY & CLINICAL DATA PBGM01 continues to have a
Slide 21: Initial Evidence of Improved Survival vs. Natural History
21 Initial Evidence of Improved Survival Among Study Participants vs. Natural History * 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). Interim data as presented on August 7, 2023 0.0 0.2 0.4 0.6 0.8 1.0 0
Slide 22: Dose 2 Robust Increases in CSF β-Gal Activity and Decreases in GM1 Gangliosides
22 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 23: Imagine-1 Progressing Well Against Key Study Objectives
23 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 24: PBGM01 Program Anticipated Next Steps
24 PBGM01 Program Anticipated Next Steps • Treated first patient at Dose 3 in July 2023 • Plan to share initial safety and biomarker data from Dose 3 by mid-2024 • Analyze data from Cohorts 1-6 to establish safety/tolerability profile and therapeutic potential of each dose • Continued interactions w
Slide 25: Looking Ahead
Looking Ahead Passage Bio Life-transforming therapies
Slide 26: Key Milestones
26 TIMING MILESTONE FTD-GRN 4Q 2023 Initial safety and biomarker data from three Cohort 1 patients GM1 Feb 2023 Additional safety and biomarker data from Cohorts 1–3 presented at WORLDSymposium Mid 2023 Initial safety and biomarker data from Cohort 4 (early infantile, high dose) 2H 2023 Dose first p
Slide 27: Our Vision
27 Our Vision To fulfill the promise of genetic medicine by developing transformative therapies for people with devastating CNS diseases Two exciting lead gene therapy programs in FTD and GM1 Innovative research partnership with Penn’s Gene Therapy Program Established manufacturing and process analy
Slide 28: Thank You
Thank You passagebio.com | NASDAQ GS: PASG
Slide 29: Demonstrated Leadership
29 Demonstrated Leadership LEADERSHIP TEAM Deep experience in rare disease, CNS disorders and genetic medicines Chip Cale General Counsel & Corporate Secretary Eden Fucci SVP Technical Operations BOARD OF DIRECTORS Maxine Gowen, Ph.D. Chairwoman Athena Countouriotis, M.D. Avenzo Therapeutics Derrell