Passage Bio, Inc. · NASDAQ:PASG
Passage Bio — Corporate Update (March 2023)
33 slides from Passage Bio's corporate update, Mar 6, 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 March 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 GM1 and FTD Innovative research partnership with Penn’s Gene Therapy Program Dedicated manufacturing and process analytic
Slide 4: Advancing Two Lead Clinical Programs in 2023
4 Global Imagine-1 Dose-Escalation Study of PBGM01 Global upliFT-D Dose-Escalation Study of PBFT02 NEXT MILESTONES Initial safety and biomarker data from Cohort 1 patients in 2H 2023 GM1 GANGLIOSIDOSIS A Fatal Pediatric CNS Disease Advancing Two Lead Clinical Programs in 2023 NEXT MILESTONES Initial
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 Dedicated Suite at Catal
Slide 7: PBGM01 GM1 Gangliosidosis
PBGMOlI1 y PassageBio Life-transforming therapies GM1 Gangliosidosis
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 • Sk
Slide 10: PBGM01 Our Approach
10 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 11: Imagine-1: Global Phase 1/2 Trial with PBGM01
11 Imagine-1: Global Phase 1/2 Trial with PBGM01 8 patients dosed to-date; plan to enroll patients at higher dose (Dose 3) 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, wi
Slide 12: Key Takeaways from Cohorts 1-3 Interim Data
12 * Interim data as presented on December 14, 2022 and during 19th Annual WORLDSymposiumTM on February 24, 2023. AEs=adverse events; ICM=intra-cisterna magna. Key Takeaways from Cohorts 1-3 Interim Data* SAFETY Favorable safety profile and well-tolerated • No serious AEs related to study treatment
Slide 13: PBGM01 ICM Delivery Resulted in Dose Dependent Increases in Transgene Activity in CSF
13 *Based on preliminary data from University of Pennsylvania’s ODC Natural History Study (NHS) (NCT04041102); value range (0.3-1.81 nmol/mL/3hr) PBGM01 ICM Delivery Resulted in Dose Dependent Increases in Transgene Activity in CSF • PBGM01 administration resulted in dose-dependent increase in CSF β
Slide 14: High Dose PBGM01 Led to Dose Dependent Decreases in CSF GM1 Gangliosides
14 High Dose PBGM01 Led to Dose Dependent 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 (d
Slide 15: Patients Manifest a Wide Range of Developmental Delay at Baseline
15 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 16: Milder Developmental Delay at Dosing Associated with Improved Treatment Response
16 *The Vineland-II is caretaker-assessed. **The Bayley-III is based on direct observation by a neurodevelopmental specialist. Preliminary Trend: Milder Developmental Delay at Dosing Associated with Improved Treatment Response 0 5 10 15 20 25 Overall Developmental Age (months) 6 8 10 12 14 16 18 20
Slide 17: PBGM01 Associated with Stabilization of MRI Severity Score
17 PBGM01 Associated with Stabilization of MRI Severity Score* 0 3 6 9 12 15 18 21 0 3 6 9 12 Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6 Time from Treatment (Months) MRI Severity Score Late Infantile: Circle Early Infantile: Square Low Dose: Solid Line High Dose: Dashed Line Natural
Slide 18: Data from Cohort Will Add to Understanding of Dose and Patient Selection
18 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 19: PBGM01 Program Anticipated Next Steps
19 PBGM01 Program Anticipated Next Steps • Present initial data from Cohort 4 (early infantile, high dose) by mid-2023 • Analyze data from Cohort 4 • Due to observed dose response and the absence of safety signals, planning to treat patients at a higher dose • Expect to dose first patient at a highe
Slide 20: PBFT02 Frontotemporal Dementia — GRN
PBFT02 Frontotemporal Dementia — GRN
Slide 21: FTD-GRN: A Devastating Adult Disease
21 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 o
Slide 22: Progranulin Deficiency Contributes to Neurodegeneration
22 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 structu
Slide 23: PBFT02 Our Approach
23 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 24: PBFT02: NHP Preclinical Studies Utilizing ICM
24 PBFT02: NHP Preclinical Studies Utilizing ICM • AAV1 increased CSF PGRN levels ~5x more than AAV5 and AAVhu68 vectors, without further elevating peripheral levels • CSF delivery of PBFT02 to NHPs achieved supraphysiologic CSF levels of PGRN 1. Hinderer et al., Annals Clin Trans Neurology. 2020 Le
Slide 25: PBFT02: Higher CSF PGRN May Confer Incremental Benefits
25 PBFT02: Higher CSF PGRN May Confer Incremental Benefits Microgliosis reduction strongest at highest doses / PGRN levels (murine FTD model) Lipofuscin reduced at all doses (murine FTD model) • Lipofuscin: increased levels with lysosomal dysfunction • Microgliosis: inflammatory response to pathogen
Slide 26: upliFT-D: Global Phase 1/2 Trial with PBFT02
26 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 27: Looking Ahead
Looking Ahead PassageBio Life-transforming therapies
Slide 28: Key Milestones
28 TIMING MILESTONE 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 patient at higher dose FTD-GRN 2H 2023 Initial safety and biomarker data from Co
Slide 29: Our Vision
29 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 GM1 and FTD Innovative research partnership with Penn’s Gene Therapy Program Dedicated manufacturing and process analyti
Slide 30: Thank You
Thank You passagebio.com | NASDAQ GS: PASG
Slide 31: Demonstrated Leadership
31 Demonstrated Leadership LEADERSHIP TEAM Deep experience in rare disease, CNS disorders and genetic medicines Simona King Chief Financial Officer Mark Forman, M.D., Ph.D. Chief Medical Officer BOARD OF DIRECTORS Maxine Gowen, Ph.D. Chairwoman Athena Countouriotis, M.D. Avenzo Therapeutics Derrell
Slide 32: A Broad and Robust Pipeline with Global Rights
32 A Broad and Robust Pipeline with Global Rights Transformative therapies for CNS disorders across rare and large patient populations Program* Indication Gene Discovery Pre-clinical Phase 1/2 Pivotal PBGM01† GM1 gangliosidosis GLB1 PBFT02 Frontotemporal dementia GRN PBAL05 Amyotrophic lateral scler
Slide 33: Intra-Cisterna Magna (ICM) Administration
33 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