Vor Biopharma Inc. · NASDAQ:VOR
Vor Biopharma — Investor Presentation (December 2024)
38 slides from Vor Biopharma's investor presentation, Dec 9, 2024
Slide 1: Ambition: Curing Blood Cancers through cell and genome engineering
Exhibit 99.2 Ambition: Curing Blood Cancers through cell and genome engineering 1 December 2024
Slide 2: Disclaimer
Disclaimer This presentation (the “Presentation”) contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 about Vor Biopharma Inc. (“Vor,” “Vor Bio” or the “Company”). The words “aim,” “anticipate,” “believe,” “can,” “could,” “design,” “enable”
Slide 3: Vor Bio Clinical Strategy Thesis: Trem-cel as a Therapeutic Platform
Vor Bio Clinical Strategy Thesis: Trem-cel as a Therapeutic Platform Enabling multiple targeted therapy modalities ADCs CAR-Ts Early Clinical Strategy Current Clinical Findings • Demonstrate clinical proof-of-principle Encouraging data with commercial promise with Mylotarg as approved agent Trem-cel
Slide 4: Even After Transplant, High-Risk AML Has Poor Outcomes
Even After Transplant, High-Risk AML Has Poor Outcomes Transplant After Transplant Watchful Waiting Outcomes for High-Risk Patients 100 50 Maintenance therapy unfeasible due to drug toxicity 0 0 6 12 18 24 Araki et al. JCO 2016 Months post-transplant A mainstay treatment Frequent leukemia relapses a
Slide 5: What If Shielding Could Lead to Improved Outcomes?
What If Shielding Could Lead to Improved Outcomes? …enabling use A shielded … can shield …potentially leading of otherwise toxic graft… a blood system… to improved outcomes maintenance therapies… ADC CAR-T Required Shielded Graft Attributes Engraftment Therapeutic Index Reliably reconstitute the blo
Slide 6: What is Trem-Cel?
What is Trem-Cel? Stem cell CRISPR/Cas9 selection gene engineering • Removes T cells to reduce • High-efficiency editing of Trem-cel: Starting Material graft-vs-host disease CD33 protein Stem Cell Graft Apheresis Product from Healthy Matched Donor Shielded from • Allows for large CD34+ dose • Result
Slide 7: VBP101: Trem-cel Phase 1/2a Clinical Trial
VBP101: Trem-cel Phase 1/2a Clinical Trial Engraftment Shielding Patient Journey Transplant Decision Trem-cel Infusion Engraftment Maintenance Mylotarg Transplant-eligible Starting ~day 60 up to 8 cycles Consolidation/Salvage Conditioning AML and MDS patients 2 Dose escalation 0.5-2 mg/m at high ris
Slide 8: Trem-cel Achieved Timely Engraftment
üTherapeutic üPatient üEngraftment üShielding Index Benefit Trem-cel Achieved Timely Engraftment Neutrophil Engraftment (n=25) Platelet Engraftment (n=25) Neutrophil Engraftment Platelet Recovery Trem-cel Trem-cel 1.0 1.0 median: median: Day 9.5 0.8 Day 16 0.8 0.6 0.6 0.4 0.4 Median engraftment for
Slide 9: Trem-cel Demonstrated Shielding Across Mylotarg Doses
üTherapeutic üPatient üEngraftment üShielding Index Benefit Trem-cel Demonstrated Shielding Across Mylotarg Doses Neutrophil and Platelet Peripheral Blood Counts with Mylotarg Doses 2 0.5 mg/m 2 Platelets 1 mg/m 2 2 mg/m Each point indicates a Mylotarg dose 2 0.5 mg/m 2 Neutrophils 1 mg/m 2 2 mg/m M
Slide 10: Trem-cel Enabled Broadened Therapeutic Index for Mylotarg
üTherapeutic üPatient üEngraftment üShielding Index Benefit Trem-cel Enabled Broadened Therapeutic Index for Mylotarg C and AUC Across Mylotarg Doses max Mylotarg Pharmacokinetic Profile Mylotarg PK analysis Mylotarg Pharmacokinetic Profile (2017, FDA ODAC) n=3 n=5 n=5 Safety threshold: probability
Slide 11: Baseline Risk Factor Demographics for AML Patients: VBP101 vs. Comparators
Baseline Risk Factor Demographics for AML Patients: VBP101 vs. Comparators VBP101 AML Araki Jentzsch VBP101 AML ITT Disease Characteristic Treated with Mylotarg MRD+ Cohort (2016) Adverse Risk Cohort (2022) (n=24) (n=76) (n=271) (n=15) Cytogenetics Risk ELN 2022 Favorable 8% 13% 3% N/A Intermediate
Slide 12: Trem-cel+Mylotarg RFS Appears Favorable vs Published High-Risk AML Comparators
üTherapeutic üPatient üEngraftment üShielding Index Benefit Trem-cel+Mylotarg RFS Appears Favorable vs Published High-Risk AML Comparators Relapse-Free Survival of VBP101 (intention-to-treat) vs Araki and Jentzsch (historical controls) Median RFS P value vs Hazard HR (mo) VBP101* Ratio* (HR) 95% CI*
Slide 13: Low Rate of Relapse (2/15) Among Patients Receiving Mylotarg
Low Rate of Relapse (2/15) Among Patients Receiving Mylotarg 0 30 60 90 120 150 180 210 240 270 300 330 360 390 420 450 480 510 540 570 600 630 660 Patient withdrawal from study Engraftment Mylotarg dose Relapse CD34 boost Backup graft Off study Ongoing Long-term follow-up study Back-up graft after
Slide 14: Any Grade Treatment Adverse Events After Receiving Mylotarg (n=15)
Any Grade Treatment Adverse Events After Receiving Mylotarg (n=15) Adverse Event Grade 1 Grade 2 Grade 3 Grade 4 Hematologic Anemia - 1/15 (7%) 3/15 (20%) - Autoimmune hemolytic anemia - - 1/15 (7%) - Leukopenia - - 1/15 (7%) - Lymphocyte count decreased 1/15 (7%) - - - Lymphopenia - - 1/15 (7%) - N
Slide 15: Clinical Update Summary
Clinical Update Summary • Robust neutrophil engraftment, platelet recovery and full donor myeloid chimerism • Consistent shielding from Mylotarg-related cytopenias during repeated 2 0.5, 1, and 2 mg/m doses • Immune reconstitution, multilineage chimerism, and safety profile similar to unedited CD34-
Slide 16: Trem-cel Platform with Potential >$1B Commercial Opportunity
Trem-cel Platform with Potential >$1B Commercial Opportunity Transformative Treatment Opportunity to Replace Standard of Care Transplant o Shielded transplants to prevent on-target toxicity 8000 o Targeted treatments to improve relapse free survival 7000 AML MDS 6000 Concentrated Market Opportunity
Slide 17: Physician Feedback on Trem-cel + Mylotarg Value Proposition
Physician Feedback on Trem-cel + Mylotarg Value Proposition Trem-Cel + Mylotarg SoC Transplant Perceptions of Trem-Cel • Streamlined manufacturing with consistent engraftment • Provides protection of donor cells from on-target toxicity • Positive impact on patient outcomes and reduced GvHD 22% • Ena
Slide 18: Potential Registrational Trial Design for Trem-cel/Mylotarg
Potential Registrational Trial Design for Trem-cel/Mylotarg Patient Journey AML Myeloablative Mylotarg Key Eligibility Trem-cel Potential registrational (n~80) conditioning 30d (8 cycles) Criteria endpoint: or later Relapse-free survival • 18-70 years of age (RFS) • 8/8 HLA-matched related or unrela
Slide 19: Summary of FDA Response to Type C Meeting Request
Summary of FDA Response to Type C Meeting Request • Agreement that trem-cel engrafts neutrophils and platelets and has a similar safety profile to unedited CD34+ grafts • Agreement with the trem-cel-Mylotarg registrational clinical trial design with respect to study population, control arm, primary
Slide 20: ALLO VCAR33: CD33-Directed Healthy Donor-Derived CAR-T
ALLO VCAR33 : CD33-Directed Healthy Donor-Derived CAR-T T cells exactly matched to patient’s immune system ~7-day Healthy, stem-like cells more likely manufacturing to expand and less prone to exhaustion Cells harvested from Rapid process to Terminally frozen for Clinically validated construct: prio
Slide 21: ALLO VBP301: VCAR33 Phase 1/2 Clinical Trial
ALLO VBP301: VCAR33 Phase 1/2 Clinical Trial Patient Journey ALLO Enroll VCAR33 Infusion Day 28 Follow-up + MRD or relapsed AML Arm A: Blasts ≥ 5% nd 2 transplant following standard or Lymphodepletion if required + Arm B: MRD trem-cel transplant 3x3 dose escalation 6 starting at 1 x 10 + CAR cells/k
Slide 22: ALLO VCAR33: Encouraging Signs of In Vivo Expansion
ALLO VCAR33 : Encouraging Signs of In Vivo Expansion Peripheral Blood 40,000 6 Kymriah: Mean CAR copies in responders; 0.2-5 x 10 CAR T cells/ kg 6 Bryanzi: Median CAR copies in responders; 100 x 10 CAR T cells (flat dose) • Dose escalation schedule: 30,000 6 15,000 - 1 x 10 CAR+ cells/kg Patient 1
Slide 23: VADC45, a Novel CD45-Targeted Antibody Drug Conjugate
VADC45, a Novel CD45-Targeted Antibody Drug Conjugate CD45 is highly expressed throughout the Novel pan-CD45 heme compartment (minus mature RBCs) humanized antibody cross-reactive to NHP Clinically validated linker-payload (Immunogen, alkylating agent) DGN549 payload with cleavable linker Robust pre
Slide 24: VADC45: Potential Commercial Opportunities
VADC45: Potential Commercial Opportunities Treating Relapse - Heme Malignancies Non-Chemo Conditioning - Gene Therapies • CD45 is highly expressed in AML and DLBCL • Gene therapies such as for sickle cell urgently need non-chemo conditioning agents • Target may be oncogenic, driving tissue infiltrat
Slide 25: Single Dose of VADC45 Enabled Gene-edited HSC Engraftment
Single Dose of VADC45 Enabled Gene-edited HSC Engraftment Engraftment and Persistence of Gene-edited Stem Cells NHPs received autologous transplantation of BCL11A- edited HSCs with conditioning via chemo (busulfan) Granulocyte Gene Editing compared to single Editing Frequency in Granulocytes dose of
Slide 26: Single Dose of VADC45 Efficiently Depleted Immune Cells
Single Dose of VADC45 Efficiently Depleted Immune Cells Immune Cell Depletion from Peripheral Blood (NHP) T Cell Depletion B Cell Depletion 7 6 1x10 2.5x10 6 6 8x10 2.0x10 6 6 6x10 1.5x10 6 6 4x10 1.0x10 6 5 2x10 5.0x10 0 0.0 Pre Dose Day 13 Pre Dose Day 13 0.3 mg/kg 0.3 mg/kg Monocyte Depletion Gra
Slide 27: Next-Generation Approaches
Next-Generation Approaches Expansion into Targets Beyond CD33 additional indications Avoidance of potential Multi-targeted CAR-Ts tumor escape Broader options Multiplex-edited grafts for treatment 27
Slide 28: In Vitro PoC for Multi-Specific CAR-T: Cell Killing and Shielding
In Vitro PoC for Multi-Specific CAR-T: Cell Killing and Shielding pos pos neg neg CD33 CD33 CD33 CD33 • 2 independent T cell donors pos neg pos neg CLL-1 CLL-1 CLL-1 CLL-1 • 48h co-culture of CAR-T cells AML (HL-60) with HL60 (AML) target cells Target Cells • E:T ratio 1:1 100 Multi-Specific CAR-T c
Slide 29: Multiplex HSC Editing: Minimize Translocations
Multiplex HSC Editing: Minimize Translocations Mock Minimized Translocation + + CD33 CLL-1 0.4 Double Pos 82.6% 0.3 0.2 0.1 Base Edited - - 0 CD33 CLL-1 Simultaneous Sequential Sequential Base Editing Double KO Cas9 Cas9 Cas + Inhibitor 79.5% Genome Engineering Strategies Adapted from Precision Geno
Slide 30: Vor Bio Unique Approach to Potentially Cure Blood Cancers
Vor Bio Unique Approach to Potentially Cure Blood Cancers Trem-cel, a first-in-class investigational* shielded stem cell transplant • Reliable engraftment, robust shielding of the blood system • Platform therapy addressing >$1B potential market opportunity Trem-cel + Mylotarg combination • Broadened
Slide 31: www.vorbio.com
www.vorbio.com
Slide 32: Pipeline to Change the Standard of Care in Blood Cancers
Pipeline to Change the Standard of Care in Blood Cancers Description Preclinical Clinical Anticipated Milestones Discovery/ IND- Phase Program / Trial Modality Indication Phase 1/2 Validation Enabling 2/3 Trem-cel + Mylotarg / Shielded CD33-deleted transplant + AML, MDS VBP101 CD33-directed ADC ALLO
Slide 33: Experienced Leadership Team
Experienced Leadership Team Robert Ang, MBBS, MBA Han Choi, M.D., LL.M Eyal Attar, MD Chief Financial Officer President and CEO Chief Medical Officer John King, MBA Tirtha Chakraborty, PhD Tania Philipp Chief Commercial Officer & Head Chief Scientific Officer Chief People Officer of Business Develop
Slide 34: CD33 is Amongst Highest Quality Targets in AML
CD33 is Amongst Highest Quality Targets in AML Ubiquity of Antigen Expression (Flow Cytometry) Density of Antigen Expression (QuantiBRITE) CD33 CLL-1 CD123 EMR2 EMR2 CD33 CLL-1 CD123 100 100000 80 10000 60 40 1000 20 0 100 Vor internal data 34 D = Diagnosis R = Relapse D R D R D R D R D R D R D R D
Slide 35: CD33 Negative Cells Enriched with Mylotarg Doses
CD33 Negative Cells Enriched with Mylotarg Doses Data cut-off: 1-NOV-2024 35
Slide 36: Immune Reconstitution, Full and Sustained Myeloid Chimerism, and CD33-negative Myeloid Cells Are Observed
Immune Reconstitution, Full and Sustained Myeloid Chimerism, and CD33-negative Myeloid Cells Are Observed B-lymphoid Cell Count T-lymphoid Cell Count 1000 1000 CD3 800 750 CD4 600 CD8 500 400 250 200 0 0 D100 D180 M12 D100 D180 M12 16 7 1 n: 16 7 1 n: Time Post Transplant with Trem-cel Time Post Tra
Slide 37: Risk of Veno-Occlusive Disease Related to Mylotarg
Risk of Veno-Occlusive Disease Related to Mylotarg C max Probability of Veno-occlusive Disease in Patients with Prior Transplant VBP101 mean C max 2 0.5 mg/m 2 1.0 mg/m 2 2.0 mg/m C after first dose of Mylotarg (μg/mL) max Geometric mean (R/R AML) 95% CI Mylotarg ODAC 2017 37 Probability of VOD (%)
Slide 38: Selected Precedent Randomized Trials in AML
Selected Precedent Randomized Trials in AML AML Studies Transplant Studies MORPHO SIERRA ALFA-0701 Precision-T Omidubicel 131 Gilteritinib vs I-apamistamab + Daunorubicin + Orca-T transplant vs Omidubicel vs double cord Drug and placebo Flu-TBI + alloHCT vs cytarabine ± Mylotarg SoC alloHCT graft Co
Vor Biopharma — Investor Presentation (December 2024) on 6ix