Change the Normal Expose the Cancer

Change Expose the normal the cancer

Corporate Presentation December 2020

1 Confidential Disclaimer

This Presentation contains forward-looking statements that involve substantial risks and uncertainties. All statements, other than statements of historical facts, contained in this Presentation, are forward looking statements including, but not limited to, terms such as “expect,” “plan,” “anticipate,” “intend,” “target,” “project,” “contemplate,” “believe,” “estimate,” “potential” or “continue” or the negative of these terms or other similar expressions. The Company may not actually achieve the plans, intentions, or expectations disclosed in these forward-looking statements. In addition, the forward-looking statements included in this Presentation represent the Company's views as of the date of this Presentation. The Company anticipates that subsequent events and developments will cause its views to change. However when the Company may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so. These forward-looking statements should not be relied upon as representing the Company's views as of any date subsequent to the date of this Presentation. Certain information contained in this Presentation relates to or is based on studies, publications, surveys and other data obtained from third party sources and the Company's own internal estimates and research. While the Company believes these third-party sources to be reliable as of the date of this Presentation, it has not independently verified, and makes no representation as to the adequacy, fairness, accuracy or completeness of any information obtained from third party sources. In addition, the third party included in this Presentation may involve the number of assumptions and limitations, and then can be no guarantee as to the accuracy or reliability of such assumptions. Finally, while the Company believes its own internal research is reliable, such research has not been verified by any independent source.

2 Vor Bio: Engineering the Patient to Better Fight Their Cancers Changing the Paradigm of Cancer Thinking

• Clinical-stage cell therapy company with fundamentally different approach to cancer targets

ü Proprietary engineered hematopoietic stem cell transplant (eHSC) platform

ü Unlocking potential of targeted therapies with curative intent

üVOR33 eHSC completed IND-enabling studies; CD33 CAR-T in Phase 1/2

üSingle company solution combining our eHSC and CAR-T into Treatment System

• Platform with broad potential across hematological malignancies

• Experienced and proven management team

• Recent $110M Series B financing from blue-chip investors

3 Vor Senior Team Members

Robert Ang, MBBS, MBA Tirtha Chakraborty, PhD Nathan Jorgensen, PhD President and CEO Chief Scientific Officer Chief Financial Officer

• CBO, Neon Therapeutics • VP Cell Therapy Research, Sana • Healthcare Portfolio Sr Manager, Qatar • SVP, BD Bavarian Nordic Biotechnology Investment Authority (QIA) • VP Med Affairs & BD, Cadence • Head of Hematology and Program Lead, • Snr Research Analyst, Calamos Investments Pharmaceuticals CRISPR Therapeutics • Research Analyst, Stifel Nicolaus • Frazier Healthcare Ventures, BCG • Group Leader mRNA Sciences, • Scientist, Columbia University Moderna Therapeutics

Sadik Kassim, PhD John King Amy Mendel, JD Chief Technology Officer Chief Commercial Officer Chief Legal Officer

• Exec Director Process Design, Kite • CCO, Ra Pharma • SVP IP, Ohana Biosciences • CSO, Mustang Bio • VP U.S. Neurology Business Unit, • SVP IP, Evelo Biosciences • Head of Analytical Development, Head of Global LAL-D Franchise, Head of • VP and Assoc GC, IP & Licensing, Ziopharm Novartis CAR-T Global Hematology Franchise, Alexion Oncology • Process development, NCI CAR-T, TCR, TIL • Product Director of Enbrel, Wyeth Pharmaceuticals

Tania Philipp Bob Pietrusko, PharmD Christopher Slapak, MD VP, Head of People Chief Regulatory & Quality Officer Chief Medical Officer

• VP HR, Tango Therapeutics • SVP Reg & QA, Voyager • VP Early Phase Development Oncology, • Exec Director HR, Bavarian Nordic • VP Reg & Quality, ViroPharma Eli Lilly and Co., SVP Imclone • Director HR, Mendel Biotechnology • SVP Reg, Millennium Pharmaceuticals • Ass’t Professor, Dana-Farber Cancer Institute • Assoc Director HR, Sunesis • VP Anti-infective and Anti-viral, • Assoc Clin Professor of Medicine and SmithKline Beecham Pharmacology, Indiana Univ School of Medicine

4 Traditional Tumor Target Paradigm Limited by On-Target Toxicity

The Challenge of Targeted Therapies: CD33-Targeted Therapies To identify and kill tumor cells while avoiding or minimizing damage to healthy cells Company Drug Name Modality Status Marketed Antibody-drug On-target toxicity with Pfizer Mylotarg conjugate neutropenia and thrombocytopenia

Seattle Antibody-drug Failed in Phase 3 due to Cancer cell Healthy cell SGN-CD33A target target Genetics conjugate safety issues expression expression Single agent failed in Phase Actinium Actimab-A Radio ligand 2 due to safety issues

Antibody-drug Immunogen IMGN779 Discontinued in Phase 2 conjugate

AMG 330, Bispecific Amgen In Phase 1 development AMG 673 antibodies Overlapping expression Bispecific Janssen JNJ-67571244 In Phase 1 development leading to on-target toxicity antibody

5 The Vor Platform: Changing the Tumor Target Paradigm

Vor Platform Traditional Vor Paradigm: Paradigm Engineered HSCs

Hematopoietic Genome Cancer cell Healthy cell Stem Cells Engineering Cancer cell Healthy cell target target target target expression expression expression expression

• Designed to unlock the true potential On-target toxicity Targeted of targeted therapies Therapies • Scalable platform potentially applicable across hematological malignancies and beyond

6 Engineering the Patient to Make Treatment-Resistant Transplant

Current Standard of Care THERAPY TARGETED Susceptible Marrow following induction & myeloablation

TRANSPLANT Limiting Treatment Opportunities Traditional Hematopoietic Stem Cells Matched (HSCs) Healthy Patient Donor

Editing Opportunity TARGETED THERAPY TARGETED Treatment-resistant Marrow Unlocking Potential of TRANSPLANT Vor Targeted Therapies Matched Engineering Healthy Process Donor removing or modifying Engineered Patient: surface targets Engineered Recipient with HSCs (eHSCs) engrafted eHSCs

7 AML: Large Unmet Need

Post-Transplant AML Relapse common form of acute 1.0 MOST leukemia in adults 0.8 Status at Time of Transplant 42,500 new each year in the Remission (MRD+) United States, 0.6 Active disease diagnoses Europe, and Japan 0.4 Remission (MRD–) Average five-year survival rate is less than 30% 0.2 Cumulative Incidence of Relapse of Incidence Cumulative 0.0 For healthier patients, standard of 0 2 4 6 8 care is intensive chemotherapy Years Since HSCT Araki et al, JCO 2016 followed by hematopoietic stem cell transplant (HSCT) In relapsed patients, 2-year survival rate is <20%

8 CD33 Among the Most Attractive Targets in AML

Expression in Leukemic CD34+CD38- Cells Expression in Bulk AML Population (“Leukemic Stem Cells”)

Perna, Sadelain et al, Cancer Cell 2017

9 Establishing eHSC as Standard of Care and Enabling Treatment Combos

Near-Term Development Potential Future Development

VOR33 – CD33Del Allogeneic eHSC • Expected initial engraftment and protection data VOR33/CD33 CAR-T Treatment System within 12 months of FPI – potentially validating for eHSC Transplant Companion Therapeutic VOR33 and broader eHSC approach VOR33 CD33 CAR-T

CD33-Directed CAR-T • Currently enrolling ped Ph1/2 R/R AML study Other Possible Novel Treatment Combinations • Planning adult Ph1 R/R AML study • In process development using allogeneic cells Potential New Standard of Care Companion Therapeutics eHSC • Bispecific T cell engagers • CAR-NKs Transplants • Antibody-drug conjugates

10 VOR33 (CD33Del eHSC): Proof of Concept

Validation from two independent labs

Mukherjee lab Gill lab Kiem lab

Institution

Protect cells in vitro ✓ ✓ ✓ Vor Bio Scientific Founder Protect cells in vivo ✓ ✓ ✓ Dr. Siddhartha Mukherjee Preserve cell populations and function ✓ ✓ ✓ • Associate Professor of Medicine in the Division of Hematology and Oncology at Columbia University Safety in non-human primates N/A ✓ N/A • Laboratory research focus: biology of normal and malignant blood development, with focus on AML Borot et al, Kim et al, Humbert et al, • Author of The Emperor of All Maladies: A Biography of PNAS 2019 Cell 2018 Leukemia 2018 Cancer and The Gene: An Intimate History

11 Strongest Supportive Evidence: Human Genetics

65 individuals with homozygous loss-of-function mutations in CD33 gene

in Genome Aggregation Database

http://gnomad.broadinstitute.org

12 VOR33 (CD33Del eHSCs): No Observed Impact on Cell Populations or Function Xeno-transplant Mouse Model: 16-week Bone Marrow In Vitro Cell Function Assays

No change in nucleated bone No change in No change in phagocytosis marrow cell frequency B cell frequency 100 100 ns 100 100 ns ns 80 Mock EP Mock EP 80 80 CD33Del 80 80 g811 60 + + 60 60 60 60 40

40 40 40 40 ns %hCD45 %hCD19 %hCD45+ %hCD45+ %CD19+ %CD19+ 20 % Phagocytosis 20 20 20 20 0 0 0 +E.coli +E.coli 0 0 0 +CytoD ControlControl 811 eHSC 81137 3751 51 ControlControl 811 eHSC 81137 5137 51

No change in myeloid cell frequency No change in cytokine production TNFα IL-6 MIP-1α 10 10 20 20 ns ns ns 10000 ns 1000000 ns 100000 100000 ns 8 8 10000 15 15 1000 + 10000 ns + ns 6 6 ns 1000 100 1000 10 10 pg/mL ns 100 hCD14+ hCD14+ 4 4 100 hCD11b+ hCD11b+

%hCD14 %hCD11b ns % % 10 % % 5 5 10 10 2 2 1 1 1 Basal LPS R848 Basal LPS R848 Basal LPS R848 0 0 0 0 ControlControl 811 eHSC 81137 3751 51 ControlControl 811 eHSC81137 5137 51 n=3 per group; ns=not significant (p>0.05) Mock EP CD33Del

13 n=15 per group BM-CD14_

VOR33 (CD33Del eHSCs): Resistance to CD33 Therapy

In Vitro In Vivo

40 100 100 WT CD33Mock ) Mock + )

+ DEL 80 80 CD33CD33DelDEL CD3330

60 60 20 (% of hCD45

40 (% of hCD45 40 Cells % Live + + % Live Cells % Live Cells 10

20 20 CD14 CD14

0 0 0 0 1 VhVh MylotargGO VhVh MylotargGO 0.0 0.1 1.0 0.0 0.10.1 1.0 10 10.0 10.0 100 100.0 100.0 1,000 Del 1000.0 1000.0 10,000 Mock-electroporated CD33 cellsDel 10000.0 10000.0100,000 Mock EP CD33 100000.0 100000.0 wild type cells Mylotarg (ng/mL) Mylotarg (ng/ml)Mylotarg (ng/ml)

14 VOR33: Streamlined Cell Manufacturing Process

Overnight Material Cell Genome Overnight shipped preparation selection engineering shipped

Engineered Hematopoietic Stem Cells (eHSCs) T cell Starting Material fraction Potential VOR33 eHSC Drug Product Apheresis Product material for Ready for from Healthy CAR-T Patient Dosing Matched Donor VOR33: ~3-day production process; 7–10-day vein-to-vein time

ü No new genetic material nor viral vectors ü No cell expansion

15 CD33 Can Be Efficiently and Reproducibly Removed

Efficient CD33 Removal Largely Biallelic Removal

10%

88%

Donor #Donor #: gRNA: Lot 1 Lot 2 No editing Monoallelic Biallelic

• Enriched stem cells from six independent healthy donors • Allelic editing analysis in single cell derived colonies • Two separate lots of gRNA • 84 total colonies analyzed

16 VOR33 First-in-Human Clinical Study Outline

Patient Journey Three key endpoints Eligible AML patients following induction and 1 VOR33 engraftment consolidation chemo 2 Mylotarg protection

Donor Journey 3 Relapse-free survival

Identified matched Myeloablative Anti-CD33 Therapy donor Conditioning Mylotarg Treatment Expected Clinical Trial Sites: • MSKCC (NY) • Fred Hutchinson Cancer Ctr. (WA) Stem cell • Hackensack/Theurer Cancer Ctr. (NJ)* VOR33 VOR33 At Day 60 or mobilization and Manufacturing Infusion earlier upon relapse • Miami Cancer Inst. (FL)* harvest • CWRU/Seidman Cancer Ctr. (OH)* • UC San Diego Cancer Ctr. (CA)* • Hopital Maisonneuve-Rosemont (Montreal)

* Use central IRBs and willing to begin process prior to IND approval 17 CD33-Directed CAR-T

CD33 CAR Construction

Lintuzumab binder CD28 CD3 zeta

Same antibody binder used in CD28 costimulatory domain achieved SGN-CD33A (vadastuximab talirine) superior preclinical activity vs. 4-1BB from Seattle Genetics Devised by renowned T cell expert Dr. Terry Fry Exclusively licensed from the National Institutes of Health

Development Strategy

Evaluation of Bridge-to-Transplant Monotherapy Evaluation of Safety and Preliminary Efficacy VOR33/CD33 CAR-T Treatment System

• Multi-site Phase 1/2 pediatric trial in R/R AML • VOR33 eHSC transplant - Current sponsor: Center for International Blood and Marrow • Administer CAR-T in post-transplant Transplant Research setting with curative intent • Phase 1 adult trial in R/R AML (in planning)

18 Vor AML Platform – Potential US Reimbursement Pathways

Medicare

eHSC CAR-T Carve-out for actual cost of stem NEW 2021 Inpatient MS-DRG 018 (or new MS-DRG) cell acquisition and processing Prospective Payment +/- OR Systems (IPPS) Ruling New Technology Add-on Payment for Medicare New Technology Add-on Payment (NTAP) (NTAP)

Commercial Payors

Negotiated case rate, incremental carve-out, or outcomes-based agreement

19 Vor’s Technology-Driven Pipeline Vision

Potential Future Vor platform

Vor -KO HSC platform Gene insertion, correction, Current chimeric selection, non- Single/Multiplex HSC Hematological Single Gene KO Gene KO (malignant and rare) and AML AML, MM, CLL, MDS, non-hematological diseases T cell malignancies Single targets Gene editing and gene CD33, CD123, CLL-1 Single/Multiplexing therapy

20 CD123 or CLL-1-Edited eHSCs: Normal Differentiation and Function, Target-specific Protection

Protection from CD123 CAR-T

✱ ✱ 120 120 Engineering P<0.05 100 100 ü Over 80% editing efficiency Target cell: Target cell: 80 80 WT WT 60 60 CD123Del CD123Del Engraftment 40 40 20 20 Target cell survival (%) Target cell survival (%) survival cell Target ü No change in long-term engraftment in mouse models (%) survival cell Target 0 0 ü No change in multilineage leukocyte distribution Mock CAR WildMockCD123CAR type CARCD123Del CD123CAR

Protection from CLL-1 CAR-T Function ✱✱ ✱✱ 120 120 P<0.01

ü No change in phagocytosis 100 100 Target cell: Target cell: ü No change in IL-6 production 80 80 WT WT 60 60 CLL-1Del CLL-1Del ü No change in TNF-α production 40 40

20 20 Target cell survival (%) Target cell survival (%) survival cell Target Target cell survival (%) survival cell Target 0 0 Mock CAR WildMock CLL-1CARtype CARCLL-1Del CLL-1CAR 21 ✱✱ ✱✱

✱✱ ✱✱ ✱✱✱ ✱✱ ✱✱ ✱✱✱

✱✱ ✱✱✱ ✱✱ ✱✱ ✱✱ ✱✱✱ ✱✱ ✱✱ CD33/CLL-1 Multiplex Editing Results in Protection from CAR-T Cytotoxicity 120 ✱✱✱ ✱✱ 120 ✱✱ ✱✱✱ ✱✱ ✱✱ ✱✱ Target cell: ✱✱ Target cell: 100 Protection100 from Dual CAR-T Killing ✱✱ WT ✱✱ WT 80 8080 • Dual editing of CD33 and CLL-1 CD33Del CD33Del in the same HSPCs via sequential CRISPR/Cas960 editing 6060 CLL-1Del CLL-1Del

• In40 vitro application of dual CAR-Ts 4040 CD33DelCLL-1Del CD33DelCLL-1Del • Anti-CD33 • Anti-CLL-1 20 (%) Survival Cell 2020 Target cell survival (%) survival cell Target Target cell survival (%) survival cell Target 0 00 Del Del Del -1 -1 CD33 CLL CLL Wild Type Del

CD33 Effector : Target = 1:1 CD33CAR CD33CAR Mock CAR CLL-1CAR MockCARpool CAR CLL-1CAR CARpool 22 CD33 CLL-1 CD33 CLL-1 $152M Raised from Blue-Chip Investors

• $42M Series A round announced Jan 2019 • $110M Series B round announced July 2020

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23 Vor Bio: Engineering the Patient to Better Fight Their Cancers Changing the Paradigm of Cancer Treatment