Vor Biopharma Inc. · NASDAQ:VOR
Vor Biopharma — Investor Presentation (January 2024)
36 slides from Vor Biopharma's investor presentation, Jan 5, 2024
Slide 1: Curing blood cancers through cell and genome engineering
January 2024 Ambition: Curing blood cancers through cell and genome engineering Exhibit 99.1
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: Our Vision: Cure Blood Cancers Through Cell and Genome Engineering
Our Vision: Cure Blood Cancers Through Cell and Genome Engineering Unique approach Positive clinical proof of concept VCAR33ALLO as of Sept. 30, 2023 Cash runway into 2H 2025 $160M In-house GMP manufacturing facility *tremtelectogene empogeditemcel, formerly VOR33 $160M in cash, cash equivalents and
Slide 4: Current AML Disease State and Standard of Care
Current AML Disease State and Standard of Care Conditioning Mobilize and collect stem cells from matched healthy donor Transplant Remission (MRD-) 2 0.8 Years Since HSCT Active disease Remission (MRD+) 0.0 0.2 0.4 0.6 0 Cumulative Incidence of Relapse 1 Status at Time of Transplant1 Despite transpla
Slide 5: Clear Unmet Need in AML
Clear Unmet Need in AML ~200K Post-transplant relapse, with <20% two-year survival3,4 50% Increase in # of AML transplants over the last 10 years2 ~20,000 People in the U.S. diagnosed with AML annually1 AML Transplants per year (U.S.)2 ~4,000 ~40% ~40% 1 American Cancer Society 2023 2 Current use an
Slide 6: Changing the Thinking on Tumor Targeting
Changing the Thinking on Tumor Targeting Cancer antigens also expressed on healthy cells Biology: Overlapping Targets Limits treatment opportunities leading to poor outcomes Problem: On-target Toxicity Shielded transplants allowing therapies to be cancer-specific Solution: Shielded Transplants
Slide 7: The Vision: eHSC + CAR-T Treatment Systems
The Vision: eHSC + CAR-T Treatment Systems CD33-directed antibody-drug conjugate CD33-directed transplant donor CAR-T therapy Clinical proof of concept Engraftment Heme protection VCAR33ALLO Healthy donor source, stemlike phenotype Tolerized to new marrow VCAR33AUTO Phase 1/2 NMDP-sponsored trial Ad
Slide 8: Expanding Pipeline Driven by Innovative Platform
Description Preclinical Clinical 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, MPN MDS, MPN VCAR33ALLO (allogeneic) / VBP301 CD33-directed transplant donor CAR-T A
Slide 9: Proprietary Dual Cell Product Potential
Proprietary Dual Cell Product Potential Trem-cel Starting Material Apheresis Product from Healthy Matched Donor Trem-cel: CD33-deleted Shielded HSC Product VCAR33ALLO: CD33-targeted Transplant Donor CAR-T Therapy Cell selection Lentivirus transduction T cells CAR-T VCAR33ALLO Material preparation Ce
Slide 10: Trem-cel + Mylotarg
Trem-cel + Mylotarg CD33-directed antibody-drug conjugate CD33-directed Transplant Donor CAR-T therapy Clinical proof of concept Engraftment Heme protection VCAR33ALLO Healthy donor source, stemlike phenotype Tolerized to new marrow VCAR33AUTO Phase 1/2 NMDP-sponsored trial Addresses tumor heterogen
Slide 11: VBP101: Trem-cel + Mylotarg Phase 1/2a Clinical Trial
VBP101: Trem-cel + Mylotarg Phase 1/2a Clinical Trial Transplant Decision Infusion Donor Journey Related Unrelated Maintenance Mylotarg Manufacturing vein-to-vein 7-10 days Unedited back-up graft Transplant-eligible AML patients at high risk of relapse Trem-cel Manufacturing ~7-day process Engraftme
Slide 12: Patient Characteristics
Patient Characteristics Pt Age/ Sex Disease and Genetics Weight Donor, Dose, CD33 gene-editing efficiency 1 64/F AML-MRC Highly complex cytogenetics; CR2; TP53 mutation MRD: 1.8% 69.9 kg 10/10 HLA MUD 7.6 × 106 CD34 cells/kg, 88% CD33 gene editing 2 32/M AML after myeloid sarcoma resected from abdom
Slide 13: Patient Clinical Timelines (Patients 1-8)
Patient Clinical Timelines (Patients 1-8) Patients Ineligible for Mylotarg: Patient 2 Secondary graft failure in context of prior sepsis, TMP-SMZ/possible DRESS and persistent hKU1 coronavirus infection. Graft failure resolved after back-up graft given. Patient 3 Immune thrombocytopenia. Resolving a
Slide 14: Highly Efficient Removal of CD33 from Donor HSCs
Highly Efficient Removal of CD33 from Donor HSCs Proof of Concept: Successful Engraftment of CD33-Deleted HSCs CD33 editing efficiency (%) Arrows indicated day of individual patient neutrophil engraftment Neutrophil engraftment = 3 days ≥ 500 cells/L *Luznik L. et al. J Clin Oncol 2022;40(4):356–368
Slide 15: Mylotarg Causes Deep Cytopenias Across Various Regimens
Mylotarg Causes Deep Cytopenias Across Various Regimens Fostvedt et al. Clin Pharm Thera 2019;106(5):1006-1017 Platelet counts (cells/µL) 1000 10000 100000 10000 1000 100 10 Neutrophil counts (cells/µL)
Slide 16: Evidence of Protective Effect from Mylotarg at 0.5 mg/m2
Evidence of Protective Effect from Mylotarg at 0.5 mg/m2 Mylotarg C1 Start: Pt 1 D+68; Pt 5 D+74; Pt 6 D+66 post-HCT Day from first Mylotarg dosing Mylotarg dose
Slide 17: Enrichment of CD33-negative Cells following Mylotarg
Enrichment of CD33-negative Cells following Mylotarg Myeloid Cells (Peripheral Blood) Days from first Mylotarg dosing Mylotarg dose
Slide 18: Patients 1, 5, 6: PK after 1st Dose of Maintenance Mylotarg
Patients 1, 5, 6: PK after 1st Dose of Maintenance Mylotarg Pharmacokinetics VBP101 Relapsed/Refractory AML Population (Mylotarg Phase 1 Study 0903A1-101-US)1 Parameter Mean +/- SD 0.5 mg/m2 0.25 mg/m2 0.5 mg/m2 1 mg/m2 2 mg/m2 4 mg/m2 5 mg/m2 Cmax (ng/mL) 236 (+/- 151) 15 28 50 411 611 1,325 AUCinf
Slide 19: VCAR33
VCAR33 CD33-directed antibody-drug conjugate CD33-directed Transplant Donor CAR-T therapy Clinical proof of concept Engraftment Heme protection VCAR33ALLO Healthy donor source, stemlike phenotype Tolerized to new marrow VCAR33AUTO Phase 1/2 NMDP-sponsored trial Addresses tumor heterogeneity and pote
Slide 20: A New Way of Generating CAR-T Therapy
A New Way of Generating CAR-T Therapy T cells exactly matched to patient’s new immune system, more likely to persist Stem-like, CAR-T cells more likely to expand and less prone to exhaustion Poor expansion and persistence Poorer clinical durability Exhausted, depleted T cells High manufacturing fail
Slide 21: 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 SOC transplant 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 d
Slide 22: VCAR33AUTO Shows Signs of Activity; VCAR33ALLO Potentially More Active
VCAR33AUTO Shows Signs of Activity; VCAR33ALLO Potentially More Active Autologous starting material 6-site IST Young adults and children (median 16 y, range 1-35) Academic manufacturing process Accepted for oral presentation at ASH N=24 enrolled, 19 infused Manageable tox (n=4 with CRS ≥ Grade 3) Tr
Slide 23: Moving Beyond Proof of Concept to Pivotal
Moving Beyond Proof of Concept to Pivotal Targeting Short Registrational Pathway R/R AML Single Arm Pivotal Trials Fast Track granted on basis of trem-cel heme protection Exploring heme protection endpoints with agency Agent Indication # pts Endpoint Ivosidenib IDH1, Agios R/R AML 174 CR 25% CRh 8%1
Slide 24: Trem-cel and VCAR33: Defining Success in 2024
Trem-cel and VCAR33: Defining Success in 2024 Based on discussions with KOLs and our clinical investigators, even a single patient with clinical activity and heme protection may provide validation of the approach Expect clinical validation in 2024 Opportunity Activity Benchmark Evidence of clinical
Slide 25: Significant Clinical Progress and Upcoming Milestones
Mylotarg dosing escalated to next dose level of 1.0 mg/m2 Multiple therapeutic options enabled for patients who relapse following trem-cel transplant: Induction-course Mylotarg VCAR33ALLO Upcoming Milestones Significant Clinical Progress and Upcoming Milestones Trem-cel Potentially superior transpla
Slide 26: Next-generation Approaches
Next-generation Approaches CD33-directed antibody-drug conjugate CD33-directed Transplant Donor CAR-T therapy Clinical proof of concept Engraftment Heme protection VCAR33ALLO Healthy donor source, stemlike phenotype Tolerized to new marrow VCAR33AUTO Phase 1/2 NMDP-sponsored trial Addresses tumor he
Slide 27: In Vitro Proof of Concept for Multi KO Target Cell + Multi-Specific CAR-T
In Vitro Proof of Concept for Multi KO Target Cell + Multi-Specific CAR-T CD33 and CLL-1 Dual-CAR-T Active Against Wild Type and Single Knock-out Target Cells 0 40 80 100 20 60 % of Viable Cells Tandem CAR-T Untransduced T Cells Tandem CAR-T Untransduced T Cells Tandem CAR-T Untransduced T Cells Tan
Slide 28: Multiplex Editing: Proprietary Capabilities
Multiplex Editing: Proprietary Capabilities Minimize Translocations and Protects from CAR-T Effector : Target = 1:1 Target Cell Survival (%) Wild Type CD33Del 0 40 60 80 20 CLL-1Del CD33DelCLL-1Del Translocation (%) Simultaneous Cas9 0.3 0.4 0.2 0.1 0 Sequential Cas9 Sequential Cas + Inhibitor Base
Slide 29: Our Vision: Cure Blood Cancers Through Cell and Genome Engineering
Our Vision: Cure Blood Cancers Through Cell and Genome Engineering Unique approach Positive clinical proof of concept VCAR33ALLO as of Sept. 30, 2023 Cash runway into 2H 2025 $160M In-house GMP manufacturing facility *tremtelectogene empogeditemcel, formerly VOR33 $160M in cash, cash equivalents and
Slide 30: vorbio.com
W vor www.vorbio.com
Slide 31: Experienced and Passionate Leadership Team
Experienced and Passionate 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 De
Slide 32: Mylotarg at 0.5 mg/m2 Equivalent to ~3 mg/m2 in CD33-negative Hematopoiesis
Data from 3.0 mg/m2 mean (+/- ci) data digitized from simulations presented in Hibma et al, 2019 VBP101 R/R AML Mylotarg at 0.5 mg/m2 Equivalent to ~3 mg/m2 in the Context of CD33-negative Hematopoiesis Mylotarg Plasma Concentration (ng/mL) Time (h)
Slide 33: Safety Events Possibly Related to Trem-cel or Mylotarg
Safety Events Reported as Possibly Related to Either Trem-cel or Mylotarg (AE ≥ Grade 3 or any Grade SAE) Adverse Event Max Grade Related to Trem-cel (# of events) Related to Mylotarg (# of events) SAE (# of events) Anemia 3 1 — — Neutropenia 3 1 — — Thrombocytopenia 3 2 — — Graft Failure 4 1 — 1 Pl
Slide 34: Potential Reimbursement Pathways
Potential Reimbursement Pathways MS-DRG 014 applies to allogeneic bone marrow transplants Section 108 (2020) provides new cost-based reimbursement for 100% of stem cell acquisition and processing Omisirge® (recently FDA-approved HSC product) priced at $338,000 Shielded Stem Cell Transplants As of 20
Slide 35: High Editing Frequency for Next-Generation Targets
High Editing Frequency for Next-Generation Targets CD34+ Editing Frequency CD5 0 40 80 100 20 60 Editing Frequency (%) Control guide T Cell Target n=9 CD123 0 40 80 100 20 60 Editing Frequency (%) Control guide Myeloid Targets n=19 n=21 n=6 CLL-1 EMR2
Slide 36: Multiplex Editing Strategies Achieve Highly Efficient Double Knock-out
Multiplex Editing Strategies Achieve Highly Efficient Double Knock-out CLL1 CD33 CLL-1 CD33 CD33-CLL-1- Double KO 79.5% CD33+CLL-1+ Double Pos 82.6% Sequential Cas9 Editing Base Editing Mock Mock Edited Edited CD33+CLL-1+ Double Pos 99.4% CD33-CLL-1- Double KO 84.3%