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Change the Normal Expose the Cancer Change Expose the normal the cancer September 2021 1 Confidential 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” or the “Company”) 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 “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “project,” “should,” “target,” “vision,” “will,” “would,” or other similar expressions. Such forward-looking statements in this Presentation include those regarding Vor’s plans, strategies and expectations for its preclinical and clinical programs, including the anticipated milestones and related catalysts of such programs. Vor may not actually achieve the plans, intentions, or expectations disclosed in these forward- looking statements. These forward-looking statements should not be relied upon as representing Vor’s views as of any date subsequent to the date of this Presentation. Factors that could cause actual results to differ include, but are not limited to, Vor’s dependence on its product candidates VOR33 and VCAR33, the risks inherent in biopharmaceutical product development and clinical trials, including the lengthy and uncertain regulatory approval process, uncertainties related to the timing of initiation, enrollment and completion of clinical trials, whether the clinical trials will validate the safety and efficacy of VOR33 and VCAR33 in acute myeloid leukemia or other indications, and the impact of the COVID-19 pandemic on Vor’s business, operations, strategy and anticipated milestones, among others. These and other risks are described in greater detail under the caption “Risk Factors” in Vor’s reports filed with the Securities and Exchange Commission (“SEC”), and in other filings that Vor may make with the SEC in the future. We may not actually achieve the plans, intentions or expectations disclosed in our forward-looking statements, and you should not place undue reliance on our forward- looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward- looking statements we make. In addition, the forward-looking statements included in this Presentation represent our views as of the date of this Presentation. We anticipate that subsequent events and developments will cause our views to change. We undertake no obligation to update or revise any forward-looking statements, whether as a result of new information, the occurrence of certain events or otherwise. 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 information included in this Presentation may involve a number of assumptions and limitations, and there can be no guarantee as to the accuracy or reliability of such assumptions. Finally, while we believe our own internal research is reliable, such research has not been verified by any independent source. 2 Vor’s Vision Cure blood cancer through transformative cell engineering Hematopoietic Genome CAR-T Stem Cells Engineering Cell Therapies VOR PLATFORM 3 Changing the Thinking on Tumor Targeting Traditional Paradigm for Vor Paradigm: Reality Drug Development Engineered HSCs (eHSCs) Target Expression Cancer cell Healthy cell Problem: few unique cancer antigens, Solution: remove target expression Philosophy: target cancer so drugs kill both cancer and healthy on healthy cells so that killing is antigens to kill cancer cells cells through on-target toxicity cancer-specific 4 Myeloid Cancer Unmet Need is Large and Increasing Most Common Form of Frequent Relapse More Allogeneic Transplants Adult Acute Leukemia Post-Transplant 5000 0.8 Status at Time of Transplant Remission (MRD+) 4000 MDS 0.6 Active disease 3000 0.4 ~20,000 – AML cases diagnosed 2000 AML Remission (MRD ) annually 0.2 1000 Annual US Allogeneic HSCT US Annual Allogeneic Cumulative Incidence of Incidence Relapse Cumulative 0.0 0 2000 2005 2010 2015 0 2 4 6 8 Years Since HSCT For patients who relapse post-transplant, 2-year survival is <20% 5 The Vision: eHSC + CAR-T Treatment Systems VOR33 Mylotarg Designed by renowned CAR-T cell expert Dr. Terry Fry Treatment-resistant 1st generation HSC transplant antibody-drug conjugate • Exclusively licensed from NIH • CAR construct in multi-site Phase 1/2 pediatric NMDP-sponsored trial in R/R AML Potential advantages for healthy VOR33 VCAR33 donor cell source Treatment-resistant Allogeneic CAR-T • Tolerized to new bone marrow HSC transplant • Healthy T cell phenotype May avoid tumor escape mechanisms Multiplex-edited Multi-specific HSCs CAR-Ts May address tumor heterogeneity Multi-treatment-resistant Abound Bio collaboration HSC transplant 6 Expanding Pipeline Driven by Innovative Platform Description Preclinical Clinical Anticipated Milestones Discovery/ IND- Program Modality Indication Phase 1/2 Phase 2/3 Validation Enabling AML with Mylotarg • 1H 2022: Initial clinical data VOR33 eHSC (CD33) MDS, MPN • Development candidate selection VCAR33 Bridge-to- • 2022: Initial monotherapy CAR-T NMDP-sponsored trial* (CD33) transplant AML clinical proof-of-concept data* VOR33 / VCAR33 eHSC / • 2H 2022: IND filing following AML Treatment System CAR-T initial VOR33 and NMDP clinical data* Discovery Programs • Leveraging our proprietary Vor platform, we have identified additional surface targets such as CD123 and CLL-1 as well as multiplex genome Vor Platform engineering approaches where multiple surface targets are removed. • Additionally, we are conducting ongoing discovery efforts on undisclosed targets for non-myeloid malignancies. AML: acute myeloid leukemia; MDS: myelodysplastic syndrome; MPN: myeloproliferative neoplasm * The VCAR33 construct is being studied in a Phase 1/2 clinical trial sponsored by the National Marrow Donor Program (“NMDP”), and the timing of data release is dependent on the investigators conducting the trial. See appendix for more information. 7 Preclinical Validation of CD33 Deletion in HSCs 1. Homing 2. Engraftment 3. Survival Migrate to bone Repopulate the blood Fully functional Resistance to marrow system blood cells toxic therapy ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ 8 VOR33: No Observed Impact on Cell Populations or Function Bone Marrow Cells B Cells Phagocytosis 80 100 100 80 80 60 Control 60 60 40 VOR33 40 40 %hCD45+ %hCD19+ 20 20 %Phagocytosis 20 0 0 0 Control VOR33 Control VOR33 +E.coli +E.coli +CytoD Myeloid Cells Cytokine Production 10 20 10,000 TNF 1,000,000 IL-6 100,000 MIP-1 ⍺ 100,000 10,000 ⍺ 8 15 1,000 10,000 6 1,000 10 100 1,000 pg/mL 100 4 100 %hCD14+ %hCD11b+ 10 2 5 10 10 0 0 0 0 0 Basal LPS R848 Basal LPS R848 Basal LPS R848 Control VOR33 Control VOR33 n=3 per group Control VOR33 9 Strongest Supportive Evidence for CD33 Dispensability: Human Genetics 65 individuals with homozygous loss-of-function mutations in CD33 gene in Genome Aggregation Database 10 VOR33: Resistance to CD33 Therapy In Vitro In Vivo 100 30 VOR33 ) 80 + 20 60 ~70-Fold (% in hCD45 40 + 10 % Live Cells 20 Control CD14 0 0 Vh Mylotarg Vh Mylotarg Mylotarg, ng/mL Control VOR33 • Engineered cells were not enriched for CD33 deletion and some cell death was expected based on residual CD33 expression • Free calicheamicin dissociated from Mylotarg may have led to non-specific cell death 11 VOR33: Streamlined Cell Manufacturing Process Hematopoietic Stem Cells Vor is Building a Fully Integrated Manufacturing Facility for eHSC and CAR-T Drug Products CAR-T Cells Overnight Material Cell Genome Overnight shipped preparation selection engineering shipped Engineered Hematopoietic Starting Material T cell Stem Cells (eHSCs) VOR33 eHSC Drug Product Apheresis Product from fraction Ready for Patient Dosing Potential Healthy Matched Donor CAR-T material VOR33: ~3-day production process; 7–10-day vein-to-vein time No new genetic material nor viral vectors No cell expansion 12 VBP101: VOR33+Mylotarg Phase 1/2a Clinical Trial VOR33 VOR33 Day 28 Anti-CD33 Transplant Decision Infusion Engraftment Therapy Transplant-eligible AML patients in Induction Consolidation Conditioning Mylotarg Treatment remission but at high Day 60 or earlier upon relapse risk of relapse Patient Journey Key Endpoints Stem Cell 1 VOR33 engraftment Screening Mobilization, VOR33 Collection ManufacturingManufacturing 2 Mylotarg protection vein-to-vein 7-10 days Donor Journey Related Unrelated 3 Relapse-free survival Back-up Marrow Clinical Trial Sites • MSKCC (NY) • Miami Cancer Inst. (FL) • Hôpital Maisonneuve-Rosemont (Montreal) • Fred Hutchinson Cancer Ctr. (WA) • CWRU/Seidman Cancer Ctr. (OH) • WashU Siteman Cancer Cntr. (MO) • Hackensack/Theurer Cancer Ctr. (NJ) • UC San Diego Cancer Ctr. (CA) 13 Potential Value Proposition and Reimbursement Pathways e ngineered for Protection Seamless Protected Curative H Integration Bone Marrow Intent Comparable engraftment Invisible and resistant to Unlock new treatments S Well-characterized,
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