Slide 1: PBGM01 Study in Infantile GM1 Gangliosidosis
PBGM01 Study in Infantile GM1 GangliosidosisInterim Safety, Biomarker and Efficacy Results from Low Dose, Late Infantile Cohort of Ongoing Imagine-1 Clinical StudyFebruary 11, 2022
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 GangliosidosisBruce GoldsmithImagine-1 Clinical Study Overview & Review of Safety, Biomarker, and Preliminary Efficacy ResultsEliseo SalinasClosing RemarksBruce Go
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 Well tolerated and positive safety profile with no serious AEs and no complications related to ICM injection No evidence of DRG toxicity based on nerve conduction studies Substantial increases in
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: Natural History of Late Infantile GM1
7 Natural History of Late Infantile GM1•Type 2 late infantile GM1 generally characterized by plateau of motor and cognitive development followed by slow developmental regression•Declines in ambulation and expressive language are often the first and most prominent clinical features•Patients experienc
Slide 8: Imagine-1: Global Phase 1/2 Trial with PBGM01
8 Imagine-1: Global Phase 1/2 Trial with PBGM01Currently enrolling Cohort 2 and Cohort 3 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 1La
Slide 9: Imagine-1 Study: Baseline Patient Characteristics
9 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)NegativeNe
Slide 10: Imagine-1 Study: Cohort Safety & Tolerability
10 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 11: Imagine-1 Study: Cohort Adverse Events
11 Imagine-1 Study: Cohort 1 Adverse Events Adverse EventClinical SeverityTreatment RelatedDiaper RashMildUnrelatedThrombocytopeniaModerateUnrelatedHeadacheModerateProcedureBruise (1-2mm)MildProcedureConstipationMildUnrelatedBruiseMildUnrelatedFall at HomeMildUnrelatedCoughMildUnrelatedAbnormal Flui
Slide 12: Cohort 1 Interim Biomarker Data
12 •CSF β-gal Activity increased in both patients•Post treatment β-gal activity above NHS patient values (Range 0.30–1.81 nmol/mL/3hr)2Cohort 1 Interim Biomarker Data 01 2 340306090120150180β - Gal Activity, CSF (nmol/mL/3hr) Time (Days)CSF β-gal+0.6+2.7 •Serum β-gal activity increased in both patie
Slide 13: Measuring Developmental Milestones
13 Measuring Developmental MilestonesVineland-II and Bayley-III scales Vineland-IIAssessed by CaregiverBayley-IIIAssessed by Trained ClinicianExample MeasurementsMotorGross MotorXXAbility to walk, run or balanceFine MotorXXAbility to squeeze toy or put piece in puzzleLanguage Receptive languageXXAbi
Slide 14: Patient 1: Vineland-II
14 Patient 1: Vineland-IIImprovement documented in all developmental areas through 9-month assessments 813182328 33381214161820222426Developmental Age (months)Chronological Age (months) Normal Fine motor Gross motor Receptive language Expressive language Personal living skills Interpersonal relation
Slide 15: Patient 1: Bayley-III
15 Patient 1: Bayley-IIIImprovement also directly observed in all developmental areas 81012 14 16 18 20 221315171921Developmental Age (months)Chronological Age (months) Normal Gross motor Fine motor Receptive language Expressive language Cognition Overall (months)Baseline3 months6 monthsPatient Age1
Slide 16: Patient 2: Vineland-II
16 Patient 2: Vineland-IIImprovement documented despite severe developmental delay at baseline 81012 14 16 18 20 2230323436Developmental Age (months)Chronological Age (months) Fine motor Gross motor Receptive language Expressive language Personal living skills Interpersonal relationships Play and le
Slide 17: Patient 2: Bayley-III
17 Patient 2: Bayley-IIIImprovement observed for motor, language, and cognitive domains 02 4 6 810 12 1430323436Developmental Age (months)Chronological Age (months) Gross motor Fine motor Receptive language Expressive language Cognition Overall (months)Baseline3 monthsPatient Age3134MotorGross motor
Slide 18: Case Study: Patient 1 (Vineland-II)
18 Case Study: Patient 1 (Vineland-II)Meaningful gains in developmental milestones Baseline9-month AssessmentGross motorTaking a few steps without supportRunning without fallingAble to climb off bedAble to balance on one footAble to move up and down stairsFine motorSometimes able to squeeze toyAlway
Slide 19: Case Study: Patient 2
19 Case Study: Patient 2•Patient 2 presented with advanced disease, showing significant developmental delays in all domains–Developmental age of 7 months vs. chronological age of 31 months•At month 4, following the 3-month Vineland and Bayley assessments, Patient 2 was clinically observed to have re
Slide 20: Initial Patients Dosed in Both Cohort 2 and Cohort 3
20 Initial Patients Dosed in Both Cohort 2 and 3 Patient 3Patient 4DiagnosisEarly Onset (Type 1) Late Onset (Type 2a)Dosing Cohort*Low dose (3.3e10 GC/g)High dose (1.1e11 GC/g)Gender FemaleFemaleAge at onset of symptoms (months)511Age at gene transfer (months)1518DBS β-Gal activity(1)(nmol/ml/hr)0.0
Slide 21: Key Takeaways from Interim Cohort Data
21 Key Takeaways from Interim Cohort 1 DataWell tolerated, demonstration of functional transgene expression, and meaningful developmental improvement BIOMARKERSPost treatment CSF and serum β-gal activity for both patients above natural history study (NHS) patient values•Increases in CSF and serum β-
Slide 22: Program Anticipated Next Steps
22 Program Anticipated Next Steps •Leverage patient identification efforts to identify future study participants Continue to enroll Cohorts 2 and 3 •2 additional sites opened since December (Canada & Brazil)•6 sites currently open, 4 additional planned Continue to open additional trial sites in mult
Slide 23: Thank you
Thank you to the patients, families, caregivers and investigators for their participation in this study.