Vor Biopharma Inc. · NASDAQ:VOR
Vor Biopharma — ASGCT 2021
21 slides from Vor Biopharma's conference presentation, May 11, 2021
Slide 1: VOR33: A Clinic-Ready CRISPR/Cas9 Engineered Hematopoietic Stem Cell Transplant for AML
VOR33: A Clinic-Ready CRISPR/Cas9 Engineered Hematopoietic Stem Cell Transplant for the Treatment of Acute Myeloid Leukemia ASGCT | May 11, 2021 John Lydeard1, Michelle Lin1, Chong Luo1, Shu Wang1, Amanda Halfond1, Mark B. Jones1, Julian Scherer1, Dane Hazelbaker1, Meltem Isik1, Azita Ghdossi1, Juli
Slide 2: Disclosures
Disclosures John Lydeard is a salaried employee of Vor Biopharma and hold an equity interest in the company. 2 Confidential
Slide 3: >60% of Patients With AML With MRD+ Remission Will Relapse Within 1 Year
>60% of Patients With AML With MRD+ Remission Will Relapse Within 1 Year After Transplantation Cumulative Incidence of Posttransplant Relapse 1.0 Cumulative Incidence of Relapse Active disease Remission (MRD+) 0.8 Remission (MRD–) Cumulative Risk of Relapse After Active Transplantation 0.6 MRD+ 0.4
Slide 4: VOR33: Engineering the Patient to Make Treatment-Resistant Transplant
VOR33: Engineering the Patient to Make Treatment-Resistant Transplant Current Standard of Care Visible Marrow TARGETED THERAPY following induction & myeloablation TRANSPLANT Traditional Hematopoietic Stem Cells (HSCs) AML Patient Pheresis Editing Opportunity “Invisible” Marrow TARGETED THERAPY TRANS
Slide 5: CD33 as a Therapeutic Target in AML
CD33 as a Therapeutic Target in AML ► Broadly expressed in AML Blasts and Leukemic Stem Cells − Expressed on normal myeloid cells ► Member of Siglec family (Siglec3), role unknown ► CD33 KO well tolerated in mouse and human − 65 individuals with homozygous loss-of-function (LOF) in gnomAD database1
Slide 6: Efficient Deletion of CD33 at Clinical Scale Manufacturing
Efficient Deletion of CD33 at Clinical Scale Manufacturing Confidential
Slide 7: VOR33: Streamlined Cell Manufacturing Process
VOR33: Streamlined Cell Manufacturing Process Material CD34+ Cell Genome Overnight Selection Overnight shipped preparation engineering shipped eHSCs Starting Material VOR33 eHSC Drug Product Apheresis product Ready for from healthy patient dosing HLA-matched donor VOR33: ~3-day production process; 7
Slide 8: VOR33 Manufacturing At Scale is Reproducible and Robust
VOR33 Manufacturing At Scale is Reproducible and Robust Cell Yield Cell Purity (T-Cell Removal) Editing ~73% Viable CellCount Viable Cell Count Viability Viability CD34 CD34 + CD3 CD3+ Editing Editing 10 100 100 10 100 80 80 8 80 x 106 cells/mL Percent Percent Percent Percent 60 60 6 60 5 %CD3 < 2%
Slide 9: VOR33: CD33 Protein Loss Upon Gene Editing
VOR33: CD33 Expression Protein Loss Upon Gene Editing Gene Editing Protein Expression 100 100 CD33 Expression, % Positive Mock Editing Frequency, % Donor 1: Mock 80 80 Donor 2: Mock 60 Donor 1: VOR33 60 Donor 3: Mock Donor 2: VOR33 Donor 1: VOR33 40 Donor 3: VOR33 40 Donor 2: VOR33 VOR33 Donor 3: VO
Slide 10: Maintenance of Hematopoietic Function in CD33 Gene-Edited Cells
Maintenance of Hematopoietic Function in CD33 Gene-Edited Cells Confidential
Slide 11: VOR33: No Observed Impact on Cell Function
VOR33: No Observed Impact on Cell Function In Vitro Cell Function Assays Phagocytosis Cytokine production 80 ns TNFα IL-6 MIP-1α Mock EP 10000 1000000 1000000 % Phagocytosis g811 60 100000 100000 1000 10000 10000 pg/mL 40 100 1000 1000 ns 100 100 20 10 10 10 0 1 1 1 +E.coli +E.coli +CytoD Basal LPS
Slide 12: VOR33: No Impact on HSC Engraftment and Differentiation in vivo
VOR33: No Impact on HSC Engraftment and Differentiation in vivo 16w • Multilineage engraftment • Bone Marrow Editing % • Hematopoietic progenitor potential ♀ NSG High Editing Maintained for Xeno-Transplant in NSG Mouse Model: 16-Week Bone Marrow 16-Weeks of Engraftment No Impact on Differentiation E
Slide 13: Pharmacology: CD33 Null Cells Are Protected From CD33-Directed Therapy
Pharmacology: CD33 Null Cells Are Protected From CD33-Directed Therapy Confidential
Slide 14: VOR33: Protected from CD33 Directed Therapy
VOR33: Protected from CD33 Directed Therapy In Vitro: Monocytes In Vivo: 16-Week Engraftment CD33WT CD33WT 100 CD33Del 40 CD33Del 50% viability 80 CD14+ (% of hCD45+) 30 % Live Cells 60 20 40 20 10 0 0 Vh Mylotarg Vh Mylotarg 0 1 0 .0 0 10 .0 10 0.0 .0 0. 0. 1. 0. 10 00 00 10 00 10 00 Mock EP VOR33
Slide 15: Safety: Toxicology and Off-Target Results
Safety: Toxicology and Off-Target Results Confidential
Slide 16: Toxicology Assessment Did Not Reveal Significant Adverse Findings for VOR33
Toxicology Assessment Did Not Reveal Significant Adverse Findings for VOR33 In life observations (every 3–6 days) Organ weights (11) Histopathology (43) • Mortality • Adrenals • Prostate • Adrenals • Pituitary • Clinical signs • Brain • Spleen • Aorta (thoracic) • Prostate • Body weights • Heart • T
Slide 17: Assessment of Off-Target Edits: No Significant Off-Target or Safety Concerns
Assessment of Off-Target Edits: VOR33 Has No Significant Off-Target or Safety Concerns Unbiased Assessment GUIDE-seq of Off-Target Sites Low frequency genomic sites identified with no perceivable safety risk In Silico Predicted Hybrid Capture NGS Off-Target Sites No reproducible and reliably edited
Slide 18: Summary
Summary • Clinical ready manufacturing process • HSC engraftment and function are unaltered despite loss of CD33 • CD33 null cells are protected from CD33-directed therapy • No toxicology or genomic off-target findings • VOR33 IND and CTA have been cleared by FDA and Health Canada, respectively • Mu
Slide 19: Acknowledgements
Acknowledgements Robert Ang Pete Cotter Kush Parmar Robert Pietrusko Brittney Pierson Jason Ruth Suzanne Pavluk Julia Etchin Aleks Radovic-Moreno Ankit Mehta Jessica Lisle Bruce Ricart Hannah Mager Roberta Toporovski Nipul Patel Tania Philipp Mike Pettiglio Kerry Chios Kienan Salvadore Hilary Eaton
Slide 20: Appendix
Appendix Confidential
Slide 21: ASGCT Abstract
ASGCT Abstract VOR33: A Clinic-Ready CRISPR/Cas9 Engineered Hematopoietic Stem Cell Transplant for the Treatment of Acute Myeloid Leukemia Introduction: AML is the most common form of adult acute leukemia, with median 5-year survival rate <30%. Allogeneic hematopoietic cell transplant (HCT) has long