Slide 1: Imagine-1 Study: Updated interim safety, biomarker, and efficacy data
Imagine-1 Study: Updated interim safety, biomarker, and efficacy data from the Phase 1/2 open-label, multicenter study of a single dose, intracisterna magna administration of PBGM01 in type I (early onset) and type IIA (late onset) infantile GM1 gangliosidosis Jeanine Jarnes, PharmD, BCOP, BCPS Adva
Slide 2: GM1 Gangliosidosis is a Continuum Disease
2 GM1 Gangliosidosis is a Continuum Disease Severity Residual Enzyme Activity1,3-5,8 Negligible ~1-5% ~3-10% Type I (Early Infantile)1 • Onset <6 months1-5 • Survival: <3 years1 • No new developmental milestones reached after 3-6 months5,6 Type IIa (Late-Infantile)3 • Onset 6-24 months3,4 • Survival
Slide 3: Imagine-1: Global Phase 1/2 Trial with PBGM01
3 Imagine-1: Global Phase 1/2 Trial with PBGM01 *Genome copies per gram of estimated brain weight. AAV, adeno-associated virus; CSF, cerebrospinal fluid; GLB1, galactosidase beta 1; IDMC, independent data monitoring committee. Vector is technology of The University of Pennsylvania (Gene Therapy Prog
Slide 4: Key Eligibility Criteria
4 Key Eligibility Criteria Early onset infantile (Type 1) • Aged ≥4 to <24 months, with onset of symptoms <6 months of age • Specific developmental milestones retained Late onset infantile (Type 2a) • Aged ≥6 to <36 months (with the exception of the low-dose Late Onset Infantile Cohort, which will b
Slide 5: Imagine-1 Baseline Patient Characteristics
5 Imagine-1 Baseline Patient Characteristics* DBS, dry blood spot. 1Lower limit of normal: <5.0 nmol/mL/h. †Positive family history. *Data cutoff of Nov 30, 2022. 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
Slide 6: PBGM01 was Well-Tolerated and Had a Favorable Safety Profile at Interim Analysis
6 PBGM01 was Well-Tolerated and Had a Favorable Safety Profile at Interim Analysis* Adverse Events Total (N=6 participants) Any adverse event 90 Any serious adverse event (unrelated to PBGM01) 5 Any treatment-emergent adverse events 80 Treatment-emergent adverse events in ≥2 participants Abdominal d
Slide 7: Patients Manifest a Wide Range of Developmental Delay at Baseline
7 Patients Manifest a Wide Range of Developmental Delay at Baseline Mild-moderate delay Developmental Delay at Baseline Marked delay 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 do
Slide 8: Preliminary Trend: Milder Developmental Delay at Dosing Associated with Improved Treatment Response
8 Preliminary Trend: Milder Developmental Delay at Dosing Associated with Improved Treatment Response *The Vineland-II is caretaker-assessed.**The Bayley-III is based on direct observation by a neurodevelopmental specialist. Data from Cohorts 1-3; data cut-off December 2022. 0 5 10 15 20 25 Overall
Slide 9: PBGM01 Associated with Stabilization of MRI Severity Score
9 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 10: PBGM01 ICM Delivery Resulted in Dose Dependent Increases in Transgene Activity in CSF
10 PBGM01 ICM Delivery Resulted in Dose Dependent Increases in Transgene Activity in CSF CSF, cerebrospinal fluid; ICM, intracisterna magna. *Based on preliminary data from University of Pennsylvania’s ODC Natural History Study (NHS) (NCT04041102); value range (0.3-1.81 nmol/mL/3hr). Data from Cohor
Slide 11: PBGM01 ICM Delivery Resulted in Dose Dependent Decreases in CSF GM1 Gangliosides
11 PBGM01 ICM Delivery Resulted in Dose Dependent Decreases in CSF GM1 Gangliosides CSF, cerebrospinal fluid. *Lang FM, et al. Mol Genet Metab.2020;129:228-235. Data from Cohorts 1-3; data cutoff December 2022. 0 High dose 600 400 200 0 0 47 375 75% drop from baseline GM1 Ganglioside, CSF Low dose G
Slide 12: PBGM01 ICM Delivery Resulted in Decreases in β-Gal Substrate Dp5 in Urine
12 PBGM01 ICM Delivery Resulted in Decreases in β-Gal Substrate Dp5 in Urine Key Points • Dp5 are O-linked pentasaccharides or (O-linked glycans) that accumulate in GM1; represent a biomarker of peripheral -gal activity* • High dose PBGM01 administration resulted in prominent decreases in urine Dp5
Slide 13: PBGM01: Summary and Future Directions
13 PBGM01: Summary and Future Directions AEs, adverse events; CSF, cerebrospinal fluid; DRG, dorsal root ganglion; ICM, intracisterna magna. Safety Favorable safety profile and well-tolerated • No serious AEs related to study treatment • No evidence of DRG toxicity • No evidence of antibody response
Slide 14: Thank You
14 Thank You Acknowledgments • Thank you to the patients, families, and caregivers for their participation in this study • Thank you to the coordinators and site study staff who are instrumental in making this work happen • Vector discovered by the University of Pennsylvania’s Gene Therapy Program •