Slide 1: PBGM01 Study in Infantile GM1 Gangliosidosis
PBGM01 Study in Infantile GM1 GangliosidosisInterim Safety and Biomarker Results from Low Dose, Late Infantile Cohort of Ongoing Imagine-1 Clinical StudyDecember 17, 2021
Slide 2: Welcome & Agenda
2 Welcome & Agenda Eliseo Salinas, M.D.Chief R&D OfficerBruce Goldsmith, Ph.D.Chief Executive OfficerExecutive Summary, Overview of GM1 Gangliosidosis & Our ApproachBruce GoldsmithImagine-1 Clinical Study Overview & Review of Cohort 1 Initial Safety and Biomarker DataEliseo SalinasClosing RemarksBru
Slide 3: Forward-Looking Statement
3 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 4: Executive Summary of Low Dose PBGM01
4 Executive Summary of Low Dose PBGM01Interim results from Cohort 1 in ongoing Imagine-1 clinical study IDMC recommends advancement to two planned cohorts which will be enrolled in parallel Well tolerated and positive safety profile with no serious AEs and no complications related to ICM injection N
Slide 5: GM1 Gangliosidosis: A Devastating Pediatric Disease
5 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 6: GM1 Gangliosidosis Disease Continuum
6 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 7: PBGM01 Supported by Compelling Preclinical Data
7 GLB1-/-mouse model•Dose-related histological correction, improvements in neurological function, and survival•Dose-dependent increases in β-gal activity in brain, CSF, serum, and critical peripheral tissues•Of the four doses evaluated, two were selected for clinical development–1.3e10 GC (dose 2):–
Slide 8: Ongoing Natural History Study
8 Ongoing Natural History Study•The University of Pennsylvania's Orphan Disease Center is conducting an ongoing natural history study (NHS) in patients with infantile and juvenile GM1•Baseline CSF and serum samples from an initial NHS patient cohort were analyzed for β-gal activity–CSF samples: 7 pa
Slide 9: Imagine-1: Global Phase 1/2 Trial with PBGM01
9 Imagine-1: Global Phase 1/2 Trial with PBGM01 COHORT 4Early Infantilen = 2DOSE 2 (1.1e11 GC/g)*DOSE 1 (3.3e10 GC/g)* Expansion CohortEarly Infantilen = 6 Expansion CohortLate Infantilen = 6 COHORT 2Late Infantilen = 2 COHORT 3Early Infantilen = 2 COHORT 1Late Infantilen = 2 IDMC review 60 days bet
Slide 10: Key Study Inclusion Criteria
10 Key Study Inclusion Criteria Early Infantile(Type 1)Late Infantile(Type 2a)Age4 –24 months6 –36 months(12 –36 months for Cohort 1)Onset of SymptomsBefore 6 monthsSpecific developmental milestones remaining6 –18 monthsSpecific developmental milestones remainingDisease Confirmation(Pre-screening)Co
Slide 11: Imagine-1 Study: Baseline Patient Characteristics
11 Imagine-1 Study: Baseline Patient CharacteristicsCohort 1 (n=2): Low dose (3.3e10 GC/g)*, Late Infantile (Type 2a) Patient 1Patient 2Gender MaleMaleAge at onset of symptoms (months)1412Age at gene transfer (months)1531DBS β-Gal activity(1)(nmol/ml/hr)0.00.2Pre-existing vector nAbs–CSF(2)NegativeN
Slide 12: Imagine-1 Study: Cohort Safety & Tolerability
12 Imagine-1 Study: Cohort 1 Safety & Tolerability No serious adverse events (SAEs) in either patient Reported adverse events (AEs) were mild-to-moderate; all moderate AEs resolved without intervention and were deemed not treatment related No complications related to ICM administration No changes in
Slide 13: Favorable Immunological Profile
13 Favorable Immunological Profile Observations following ICM administration of PBGM01: No neutralizing vector antibodies were measured in the CSF in either patient No antibodies against the transgene product developed in the CSF or serum in either patient No T-cell response was documented in either
Slide 14: CSF β-Gal Activity Increased in Both Patients
14 CSF β-Gal Activity Increased in Both PatientsPost treatment β-Gal activity above NHS patient values (nmol/mL/3hr)BaselineD30D180Patient 11.281.971.91Patient 20.713.39 •Patient 1: enzyme activity was 1.5-fold over baseline at 1 month, maintained at 6 months•Patient 2: enzyme activity was 4.8-fold
Slide 15: Serum β-Gal Activity Increased in Both Patients
15 Serum β-Gal Activity Increased in Both PatientsPost treatment β-Gal activity above NHS patient values (nmol/mL/3hr)Baseline(1)D30D90D180Patient 18.99.314.814.9Patient 28.911.0 •Patient 1: enzyme activity was 1.7-fold over baseline at 3 months, maintained at 6 months•Patient 2: enzyme activity was
Slide 16: Initial CSF GM1 Ganglioside Levels for Cohort 1
16 Initial CSF GM1 Ganglioside Levels for Cohort 1CSF GM1 Gangliosides Decreased in Patient with High β-Gal Expression 02040 60 801001201401600306090120150180nM*Time (Days) Patient 1 Patient 2 (nM)*BaselineD30D180Patient 1336261Patient 213774 •Patient 1: ~85% increase at 1 and 6 months•Patient 2: ~4
Slide 17: Key Takeaways from Interim Cohort Data
17 Key Takeaways from Interim Cohort 1 DataWell tolerated with demonstration of functional transgene expression at lowest dose •PBGM01 was well tolerated and had a positive safety profile–No complications related to ICM injection–No evidence of DRG toxicity SAFETY •Post treatment CSF and serum β-gal
Slide 18: Program Anticipated Next Steps
18 Program Anticipated Next StepsFollowing positive IDMC recommendation, Cohorts 2 and 3 are currently recruiting patients in parallel•Cohort 2: high dose, late infantile•Cohort 3: low dose, early infantileContinue to open additional trial sites in multiple countries•4 sites currently open, 6 additi
Slide 19: Thank you
Thank you to the patients, families, caregivers and investigators for their participation in this study.