Vor Biopharma Inc. · NASDAQ:VOR
Vor Biopharma — Investor Presentation (September 2024)
33 slides from Vor Biopharma's investor presentation, Sep 5, 2024
Slide 1: Ambition: Curing Blood Cancers through cell and genome engineering
September 2024 Ambition: Curing Blood Cancers through cell and genome engineering Exhibit 99.2
Slide 2: Forward-looking statements
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” “estimate,”
Slide 3: Thesis: Trem-cel as a Therapeutic Platform
Testing as monotherapy in post-transplant relapse Encouraging biomarker data at lowest dose Thesis: Trem-cel as a Therapeutic Platform Vor Bio Clinical Strategy Enabling multiple targeted therapy modalities ADCs CAR-Ts VCAR33ALLO Mylotarg Trem-cel Early Clinical Strategy Current Clinical Findings De
Slide 4: Even After Transplant, High-Risk AML Has Poor Outcomes
Transplant A mainstay treatment Even After Transplant, High-Risk AML Has Poor Outcomes After Transplant Frequent leukemia relapses and death, poor outcomes Maintenance therapy unfeasible due to drug toxicity Watchful Waiting Outcomes for High-Risk Patients Araki et al. JCO 2016 Probability of relaps
Slide 5: What If Shielding Could Lead to Improved Outcomes?
What If Shielding Could Lead to Improved Outcomes? A shielded graft… … can shield a blood system… …enabling use of otherwise toxic maintenance therapies… …potentially leading to improved outcomes ADC CAR-T Engraftment Reliably reconstitute the blood system Shielding Protect against otherwise toxic t
Slide 6: What is Trem-Cel?
What is Trem-Cel? Starting Material Apheresis Product from Healthy Matched Donor Trem-cel: Stem Cell Graft Shielded from CD33-Targeted Therapy Stem cell selection CRISPR/Cas9 gene engineering Removes T cells to reduce graft-vs-host disease Allows for large CD34+ dose to accelerate engraftment High-e
Slide 7: VBP101: Trem-cel Phase 1/2a Clinical Trial
VBP101: Trem-cel Phase 1/2a Clinical Trial Donor Journey Transplant-eligible AML and MDS patients at high risk of relapse Trem-cel Manufacturing ~7-day process Patient Journey Transplant Decision Trem-cel Infusion Maintenance Mylotarg Engraftment No delay in typical patient transplant process Starti
Slide 8: Trem-cel Achieved Timely Engraftment
Trem-cel Achieved Timely Engraftment High CD33 editing efficiency (median 89%, range 71-94%) 100% neutrophil engraftment Robust platelet recovery (median 16.5 days) Full myeloid chimerism at Day 28 Neutrophil Engraftment (n=18) Engraftment Shielding Therapeutic Index Patient Benefit * Luznik et al.
Slide 9: Trem-cel Demonstrated Shielding Across Mylotarg Doses
Neutrophil and Platelet Peripheral Blood Counts with Mylotarg Doses Trem-cel Demonstrated Shielding Across Mylotarg Doses Cell counts/µL Days from start of Mylotarg dosing 100k 10k 1000 100 10 1 Platelets 0.5 mg/m2 1 mg/m2 2 mg/m2 Neutrophils 0.5 mg/m2 1 mg/m2 2 mg/m2 1 20 40 60 80 100 120 140 160 1
Slide 10: Trem-cel Enabled Broadened Therapeutic Index for Mylotarg
Trem-cel Enabled Broadened Therapeutic Index for Mylotarg VBP101 Mylotarg PK analysis (2017, FDA ODAC) Regarding Efficacy Regarding Liver Toxicity Mean Cmax Across Mylotarg Doses Mean AUCinf Across Mylotarg Doses Approved doses Mylotarg dose (mg/m2) AUCinf (ng*h/mL) Drug exposure exceeds levels at a
Slide 11: Baseline Risk Factor Demographics: VBP101 vs. Comparators
Baseline Risk Factor Demographics: VBP101 vs. Comparators Study (Publication Year) VBP101 ITT N=18 VBP101 AT n=10 Araki MRD+ (2016) n=75 Jentzsch Adverse Risk (2022) n=271 CR1 (%) 61 50 67 90 CR2 (%) 22 40 33 10 Active Disease(%) (median blast %) 17 (16%) 10 (78%) -- -- MRD+(%) (median blast %) 11 (
Slide 12: Trem-cel+Mylotarg RFS Appears Favorable vs Published Comparators
Trem-cel+Mylotarg RFS Appears Favorable vs Published High-Risk AML Comparators Relapse-Free Survival of VBP101 (intention-to-treat) vs Araki and Jentzch (historical controls) VBP101 data cut-off: 19-JUL-2024; Adapted from Fig 2B MRD+ PFS line from Araki et al. JCO 2016; Adapted from Fig 1C, ELN 2022
Slide 13: Low Rate of Relapse (2/10) Among Patients Receiving Mylotarg
Low Rate of Relapse (2/10) Among Patients Receiving Mylotarg Mylotarg not started 0.5 mg/m2 2 mg/m2 1 mg/m2 Mylotarg On study or long-term follow-up Engraftment Mylotarg dose Back-up graft CD34 boost Relapse End of study ITP: idiopathic thrombocytopenic purpura or similar immune-mediated thrombocyto
Slide 14: Two Patients Relapsing Following Mylotarg, Both with TP53 Mutations
Two Patients Relapsing Following Mylotarg, Both with TP53 Mutations Age/ Sex AML Risk Factors Outcome and post-HCT Day Mylotarg Maintenance Dose and Cycles CD33 Expression at Time of MRD/Relapse 68/M AML-MRC, adverse cytogenetics (ELN) Complex cytogenetics High risk molecular: NRAS, ZRSR2, TET2 muta
Slide 15: Significant Unmet Need: Potential >$1B Commercial Opportunity
Significant Unmet Need Trem-cel Therapeutic Platform with Potential >$1B Commercial Opportunity *2020 - IPPS (Inpatient Prospective Payment System), MS DRG-104 – Section 108, stem cell acquisition & processing for allo-SCTs 1. CIBMTR 2020 2. CIBMTR Summary Slides 3. ACS 4. LLS 5. Polednak AP, J Regi
Slide 16: Potential Registrational Trial Design for Trem-cel/Mylotarg
Potential Registrational Trial Design for Trem-cel/Mylotarg AML (n=60-80) Key Eligibility Criteria 18-70 years of age 8/8 HLA matched related/unrelated donor Suitable for MAC AML: CD33+ AML Morphological CR1/CR2 or CRi High-risk disease (MRD+ or genetics) Potential registrational endpoint: relapse-f
Slide 17: VCAR33ALLO: CD33-Directed Healthy Donor-Derived CAR-T
VCAR33ALLO: CD33-Directed Healthy Donor-Derived CAR-T T cells exactly matched to patient’s immune system Healthy, stem-like cells more likely to expand and less prone to exhaustion Clinically validated construct: NIH study using autologous cells showed efficacy at 1 x 107 CAR+ cells/kg (2/5 assessab
Slide 18: VBP301: VCAR33ALLO Phase 1/2 Clinical Trial
VBP301: VCAR33ALLO Phase 1/2 Clinical Trial Enroll VCAR33ALLO Infusion Prior Transplant Donor MRD+ or relapsed AML following standard or trem-cel transplant VCAR33ALLO Manufacturing ~7-day process Day 28 Follow-up Consent Collect 2nd transplant if required Arm B: MRD+ Arm A: Blasts ≥ 5% 3x3 dose esc
Slide 19: VCAR33ALLO: Encouraging Signs of In Vivo Expansion
VCAR33ALLO: Encouraging Signs of In Vivo Expansion Peripheral Blood Days Post CAR-T Infusion CD33 CAR transgene copies/µg Dose escalation schedule: 1 x 106 CAR+ cells/kg 3 x 106 CAR+ cells/kg 1 x 107 CAR+ cells/kg NCI CD33CART trial (autologous) saw in vivo expansion and 2 responses out of 5 assessa
Slide 20: Introducing VADC45, a Novel CD45-Targeted Antibody Drug Conjugate
Introducing VADC45, a Novel CD45-Targeted Antibody Drug Conjugate Novel pan-CD45 humanized antibody cross-reactive to NHP DGN549 payload with cleavable linker Fc silencing to avoid effector function CD45 is highly expressed throughout the heme compartment (minus mature RBCs) Clinically validated lin
Slide 21: VADC45: Potential Commercial Opportunities
VADC45: Potential Commercial Opportunities CD45 is highly expressed in AML and DLBCL Target may be oncogenic, driving tissue infiltration, high expression and poor prognosis Opportunity: R/R AML and MDS Immune disorders that may require more holistic reset of the entire immune system Holistically re
Slide 22: 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 Tisdale et al. (NIH), preclinical data NHPs received autologous transplantation of BCL11A-edited HSCs with conditioning via chemo (busulfan) compared to single dose of VADC45 Very high mye
Slide 23: Single Dose of VADC45 Efficiently Depleted Immune Cells
Single Dose of VADC45 Efficiently Depleted Immune Cells Immune Cell Depletion from Peripheral Blood (NHP) 0 Pre Dose 5x106 4x106 2x106 Day 13 0.3 mg/kg No. Granulocyte/mL 3x106 1x106 Granulocyte Depletion 1x107 8x106 6x106 4x106 2x106 0 Pre Dose Day 13 0.3 mg/kg No. T cells/mL T Cell Depletion 0 Pre
Slide 24: Next-Generation Approaches
Next-Generation Approaches Expansion into additional indications Targets Beyond CD33 Avoidance of potential tumor escape Multi-targeted CAR-Ts Broader options for treatment Multiplex-edited grafts
Slide 25: In Vitro PoC for Multi-Specific CAR-T: Cell Killing and Shielding
In Vitro PoC for Multi-Specific CAR-T: Cell Killing and Shielding Vor internal data. UTD: untransduced T cell control, KO: knock-out AML (HL-60) Target Cells CD33pos CLL-1pos CD33pos CLL-1neg CD33neg CLL-1pos CD33neg CLL-1neg 2 independent T cell donors 48h co-culture of CAR-T cells with HL60 (AML)
Slide 26: Multiplex HSC Editing: Minimize Translocations
Multiplex HSC Editing: Minimize Translocations Translocation (%) Simultaneous Cas9 0.3 0.4 0.2 0.1 0 Sequential Cas9 Sequential Cas + Inhibitor Base Editing Genome Engineering Strategies Minimized Translocation CD33-CLL-1- Double KO 79.5% CD33+CLL-1+ Double Pos 82.6% Mock Base Edited Precision Genom
Slide 27: Vor Bio Unique Approach to Potentially Cure Blood Cancers
Vor Bio Unique Approach to Potentially Cure Blood Cancers VCAR33ALLO, differentiated transplant donor CAR-T therapy Encouraging signs of in vivo expansion with strong trial enrollment New asset: VADC45 Four distinct potential commercial opportunities Trem-cel, a first-in-class investigational* shiel
Slide 28: www.vorbio.com
W vor www.vorbio.com Confidentiat
Slide 29: Pipeline to Change the Standard of Care in Blood Cancers
Description Preclinical Clinical Anticipated Milestones Program / Trial Modality Indication Discovery/ Validation IND- Enabling Phase 1/2 Phase 2/3 Trem-cel + Mylotarg / VBP101 Shielded CD33-deleted transplant + CD33-directed ADC AML, MDS VCAR33ALLO (healthy transplant donor CAR-T) / VBP301 CD33-dir
Slide 30: Experienced Leadership Team
Experienced Leadership Team Deep Cell & Gene Therapy Expertise Robert Ang, MBBS, MBA President and CEO Tirtha Chakraborty, PhD Chief Scientific Officer Eyal Attar, MD Chief Medical Officer Tania Philipp Chief People Officer John King, MBA Chief Commercial Officer & Head of Business Development David
Slide 31: Mylotarg Enriched Blood System to ~100% CD33 Negative Cells
Mylotarg Enriched Blood System to ~100% CD33 Negative Cells Monocytes in Peripheral Blood % CD33 negative cells Mylotarg dosing cycles 2 mg/m2 1 mg/m2 0.5 mg/m2 Data cut-off: 19-JUL-2024 Engraftment Shielding Therapeutic Index Patient Benefit pre-Mylotarg
Slide 32: CD33 is Amongst Highest Quality Targets in AML
CD33 is Amongst Highest Quality Targets in AML CD33 CD123 CLL-1 EMR2 Ubiquity of Antigen Expression (Flow Cytometry) CD33 CD123 CLL-1 EMR2 D = Diagnosis R = Relapse Antigen positivity on AML blasts (%) Density of Antigen Expression (QuantiBRITE) # Antigens per cell Vor internal data
Slide 33: Risk of Veno-Occlusive Disease Related to Mylotarg
Risk of Veno-Occlusive Disease Related to Mylotarg Cmax 0.5 mg/m2 1.0 mg/m2 2.0 mg/m2 VBP101 mean Cmax 95% CI Geometric mean (R/R AML) Mylotarg ODAC 2017 Probability of Veno-occlusive Disease in Patients with Prior Transplant Cmax after first dose of Mylotarg (μg/mL) Probability of VOD (%)
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