Passage Bio, Inc. · NASDAQ:PASG
Passage Bio — Investor Presentation (January 2023)
32 slides from Passage Bio's investor presentation, Jan 9, 2023
Slide 1: Fulfilling the Promise of Genetic Medicine for Central Nervous System Disorders
© 2023 PassageBio. All rights reserved.Nasdaq: PASG Fulfilling the Promise of Genetic Medicine for Central Nervous System DisordersJanuary 2023
Slide 2: Forward-Looking Statement
2 Forward-Looking StatementThis 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 anticipated
Slide 3: Our Vision
3 Our VisionTo fulfill the promise of genetic medicine by developing transformative therapies for people with devastating CNS diseases Two exciting lead gene therapy programsin GM1 and FTD Innovative research partnership with Penn’s Gene Therapy Program Dedicated manufacturing and process analytics
Slide 4: Advancing Two Lead Clinical Programs in 2023
4 Global upliFT-D Dose-Escalation Study of PBFT02 Global Imagine-1 Dose-Escalation Study of PBGM01 NEXT MILESTONESInitial safety and biomarker data from Cohort 1 patients in 2H 2023 GM1 GANGLIOSIDOSISA Fatal Pediatric CNS DiseaseAdvancing Two Lead Clinical Programs in 2023 NEXT MILESTONESInitial saf
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 C9orf72gene 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: Unnamed•Gene
Slide 6: Leading CMC Capabilities Via a Hybrid Approach
6 Discovery UPenn GTPResearch Analytics and Vector Engineering Process/Analytic DevelopmentPassage CMC R&D Lab Proven Analytical CapabilitiesIntegrated Process DevelopmentGMP QC Capabilities Strong Regulatory CMC Scientific ExpertiseScale-up Capability GMP ManufacturingDedicated Suite at CatalentQua
Slide 7: PBGM01 GM1 Gangliosidosis
PBGMOlI1 @ 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 GLB1gene mutations characterized by destruction of neurons in the brain and spinal cord.Characterized by rapidly progressive neurological decline resulting in reduced muscle tone,
Slide 9: GM1 Gangliosidosis Disease Continuum
9 GM1 Gangliosidosis Disease Continuum GM1 Gangliosidosis is a Continuum Disease SeverityResidual Enzyme Activity (Serum) Focus of Imagine-1 TrialNegligible to 5%~ 1–5%~ 3 –10% Type 1 (Early Infantile)•Onset <6 months•Hypotonia•Neurodegeneration•Developmental regression•Seizures•Skeletal dysplasia •
Slide 10: PBGM01 Our Approach
10 PBGM01OUR APPROACHNext-generation, proprietary capsid delivers functional GLB1gene encoding β-gal to the brain and peripheral tissuesPRECLINICAL EVIDENCECompelling preclinical data in knock-out mouse model•Dose-related histological correction, improvements in neurological function, and survival•M
Slide 11: Imagine-1: Global Phase 1/2 Trial with PBGM01
11 Imagine-1: Global Phase 1/2 Trial with PBGM01Completed dosing of all patients in dose-ascending portion of study Trial DesignPhase 1/2, multi-center, open-label, dose escalation and confirmatory study Route of AdministrationIntra-cisterna magna (ICM)CapsidAAVhu68DurationTwo years, with rollover i
Slide 12: Key Takeaways from Cohorts 1-3 Interim Data
12 * Interim data as presented on December 14, 2022. AEs=adverse events; ICM=intra-cisterna magna.Key Takeaways from Cohorts 1-3 Interim Data* SAFETYFavorable safety profile and well-tolerated•No serious AEs related to study treatment•No evidence of DRG toxicity•No evidence of cell-mediated immune r
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-G
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 0200400600050100150200250300350Gangliosides, apparent nMTime (days)GM1 Ganglioside, CSF P4 Late Infantile P6 Late Infantile 0200400600 8001,000050100150200250300350Gangliosides, apparent nMTime (days)GM1 Ganglioside, CSF P1
Slide 15: Patients Manifest a Wide Range of Developmental Delay at Baseline
15 Patients Manifest a Wide Range of Developmental Delay at Baseline Patient 1Patient 2Patient 3Patient 4Patient 5Patient 6DiagnosisLate OnsetLate OnsetEarly OnsetLate OnsetEarly OnsetLate OnsetDosing CohortLow doseLow doseLow doseHigh doseLow doseHigh doseChronological age at baseline (months)14311
Slide 16: Preliminary Trend: 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 0510 15 20 2568101214161820222426283032343638404244 Overall Developmental
Slide 17: Data from Cohort Will Add to Understanding of Dose and Patient Selection
17 Data from Cohort 4 Will Add to Understanding of Dose and Patient Selection Patient 1Patient 2Patient 3Patient 4Patient 5Patient 6Patient 7Patient 8DiagnosisLate OnsetLate OnsetEarly OnsetLate OnsetEarly OnsetLate OnsetEarly OnsetEarly OnsetDosing CohortLow doseLow doseLow doseHigh doseLow doseHig
Slide 18: PBGM01 Program Anticipated Next Steps
18 PBGM01 Program Anticipated Next Steps •Present additional data from Cohorts 1-3 at 19th Annual WORLDSymposium in February 2023•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, ev
Slide 19: PBFT02 Frontotemporal Dementia — GRN
PBFT02Frontotemporal Dementia —GRN
Slide 20: FTD-GRN: A Devastating Adult Disease
20 FTD-GRN: A Devastating Adult DiseaseDEVASTATING FORM OF DEMENTIA caused by a GRNgene mutation resulting in progranulin (PGRN) deficiency and haploinsufficiency. Approximately 5–10% of FTD is caused by a GRNmutation.Disease progression is rapid and degenerative including loss of speech, loss of ex
Slide 21: Progranulin Deficiency Contributes to Neurodegeneration
21 Maintains lysosomal activityProgranulin Deficiency Contributes to NeurodegenerationFTD BrainHealthy BrainReduced progranulin leads to neuronal dysfunction and death Progranulin is critical to maintaining CNS cell homeostasis Regulates microglial activation Regulates synapse number and structure M
Slide 22: PBFT02 Our Approach
22 PBFT02OUR APPROACHProprietary construct delivers functional GRNgene encoding progranulin (PGRN) with potential therapeutic benefit of a one-time gene therapy approachPRECLINICAL EVIDENCECompelling preclinical evidence from NHP studies•Broad transduction across the brain, including high transducti
Slide 23: PBFT02: NHP Preclinical Studies Utilizing ICM
23 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 PGRN1. Hinderer et al.,Annals Clin Trans Neurology.2020Left: Two
Slide 24: PBFT02: Higher CSF PGRN May Confer Incremental Benefits
24 PBFT02: Higher CSF PGRN May Confer Incremental Benefits Microgliosis reduction strongest at highest doses / PGRNlevels(murine FTDmodel) Lipofuscin reduced at all doses(murine FTDmodel) •Lipofuscin: increased levels with lysosomal dysfunction•Microgliosis: inflammatory response to pathogenic insul
Slide 25: upliFT-D: Global Phase 1/2 Trial with PBFT02
25 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 1n = 3 COHORT 2n = 3 OPTIONAL COHORT 3n = 3 Trial DesignPhase 1/2, multicenter, open-label, dose escalation studyRoute of AdministrationIntra-cisterna
Slide 26: Looking Ahead
Looking Ahead Passage Bio Life-transforming therapies
Slide 27: Key Milestones, Pipeline and Balance Sheet
27 TIMINGMILESTONEGM1Feb 2023Additional safety and biomarker data from Cohorts 1–3 to be presented atWORLDSymposiumMid 2023Initial safety and biomarker data from Cohort 4 (early infantile, high dose)FTD-GRN2H 2023Initialsafety and biomarker data from Cohort 1patientsKey Milestones PIPELINE•Pursuing
Slide 28: Our Vision
28 Our VisionTo fulfill the promise of genetic medicine by developing transformative therapies for people with devastating CNS diseases Two exciting lead gene therapy programsin GM1 and FTD Innovative research partnership with Penn’s Gene Therapy Program Dedicated manufacturing and process analytics
Slide 29: Thank You
Thank Youpassagebio.com|NASDAQ GS: PASG
Slide 30: Demonstrated Leadership
30 Demonstrated LeadershipLEADERSHIP TEAM Deep experience in rare disease, CNS disorders and genetic medicines Simona KingChief Financial Officer Mark Forman, M.D., Ph.D.Chief Medical OfficerBOARD OF DIRECTORSMaxine Gowen, Ph.D.ChairwomanAthenaCountouriotis, M.D.AvenzoTherapeuticsDerrell Porter, M.D
Slide 31: A Broad and Robust Pipeline with Global Rights
31 A Broad and Robust Pipeline with Global RightsTransformative therapies for CNS disorders across rare and large patient populations Program* Indication GeneDiscoveryPre-clinicalPhase 1/2Pivotal PBGM01 † GM1 gangliosidosis GLB1 PBFT02 Frontotemporal dementia GRN PBAL05 Amyotrophic lateral sclerosis
Slide 32: Intra-Cisterna Magna (ICM) Administration
32 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 anesthesi