8-K

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, D.C. 20549

FORM 8-K

CURRENT REPORT

Pursuant to Section 13 or 15(d)

of the Securities Exchange Act of 1934

Date of Report (Date of earliest event reported): December 7, 2022

Vor Biopharma Inc.

(Exact name of registrant as specified in its Charter)

Delaware	001-39979	81-1591163
(State or Other Jurisdiction of Incorporation)	(Commission File Number)	(IRS Employer Identification No.)
100 Cambridgepark Drive
Suite 101
Cambridge, Massachusetts		02140
(Address of Principal Executive Offices)		(Zip Code)

Registrant’s telephone number, including area code: (617) 655-6580

(Former Name or Former Address, if Changed Since Last Report)

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instructions A.2. below):

☐ Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

☐ Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

☐ Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

☐ Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Securities registered pursuant to Section 12(b) of the Act:

Title of each class	Trading Symbol(s)	Name of each exchange on which registered
Common Stock, $0.0001 par value per share	VOR	Nasdaq Global Select Market

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).

Emerging growth company  ☒

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act.  ☐

Item 7.01 Regulation FD Disclosure

On December 7, 2022, Vor Biopharma Inc. (the “Company”) issued a press release announcing initial clinical proof-of-concept data from VBP101, its Phase 1/2a clinical trial of VOR33. A copy of the press release is attached hereto as Exhibit 99.1 and is incorporated herein by reference.

In connection with the announcement, the Company will host a call and webcast on December 7, 2022 at 8:00 a.m. ET. Call details are contained in the press release referenced above. Accompanying slides may be accessed through the “Investors” section of the Company’s website at www.vorbio.com. A copy of these slides is attached hereto as Exhibit 99.2 and is incorporated herein by reference.

The information furnished under this Item 7.01, including Exhibits 99.1 and 99.2, shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended, or subject to the liabilities of that section or Sections 11 and 12(a)(2) of the Securities Act of 1933, as amended. The information in this Item 7.01, including Exhibits 99.1 and 99.2, shall not be deemed incorporated by reference into any other filing with the U.S. Securities Exchange Commission made by the Company, whether made before or after the date hereof, regardless of any general incorporation language in such filing.

Item 8.01 Other Events

Clinical Update

On December 7, 2022, the Company announced initial clinical data from the first treated patient in its Phase 1/2a clinical trial of trem-cel (formerly VOR33) in combination with Mylotarg. A product dose of 7.6 x10⁶ CD34+ viable cells/kg, with a CD33 editing efficiency of 88% was manufactured. Following myeloablative conditioning, trem-cel was infused with no infusion reactions. The patient achieved neutrophil engraftment 10 days post-transplant which was within expectations for CD34-enriched transplants. Platelet recovery was observed on Day 22. Hematopoietic cell sub-population reconstitution was robust with over 90% of peripheral blood cells negative for CD33 expression, and 100% donor chimerism was achieved. These data provide proof-of-concept that trem-cel can engraft as expected and that CD33 does not appear to be biologically necessary for engraftment and hematopoietic reconstitution.

The patient received Mylotarg at a dose of 0.5 mg/m². At this dose, Mylotarg saturates CD33 antigen in patients with relapsed/refractory AML, and in the original Phase 1 trial of Mylotarg, neutropenia was observed across dose levels starting at 0.25mg/m² within 14 days of infusion. No treatment related adverse events and no liver enzyme changes were observed through day 20 following Mylotarg dosing. No negative impacts to neutrophil and platelet counts were observed through day 20, suggesting tolerability at this initial dose level.

The clinical trial continues to enroll patients and additional data are expected in 2023.

Regulatory Update

On August 16, 2022, President Biden signed the Inflation Reduction Act of 2022 (“IRA”) into law, which among other things, (1) directs the U.S. Department of Health and Human Services (“HHS”) to negotiate the price of certain single-source drugs and biologics covered under Medicare and (2) imposes rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation. These provisions will take effect progressively starting in fiscal year 2023, although they may be subject to legal challenges. It is currently unclear how the IRA will be implemented but is likely to have a significant impact on the pharmaceutical industry. Further, the Biden administration released an additional executive order on October 14, 2022, directing HHS to submit a report within ninety (90) days on how the Center for Medicare and Medicaid Innovation can be further leveraged to test new models for lowering drug costs for Medicare and Medicaid beneficiaries.

Item 9.01 Financial Statements and Exhibits

Exhibit No.	Description
99.1	Press release, dated December 7, 2022
99.2	Company Presentation
104	Cover Page Interactive Data File (embedded within the Inline XBRL document)

SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

	Vor Biopharma Inc.
	By:	/s/ Robert Ang
		Robert Ang
		Chief Executive Officer
Date: December 7, 2022

EX-99.1

Exhibit 99.1

First AML Patient Successfully Transplanted with Vor Bio’s

Investigational Trem-cel (VOR33) and Tolerated Mylotarg^TM

• Trem-cel (formerly VOR33) successfully manufactured and engrafted normally

• Blood counts successfully maintained following post-transplant treatment with Mylotarg

• Conference call scheduled for today, December 7 at 8:00am ET

CAMBRIDGE, Mass., Dec. 7, 2022 (GLOBE NEWSWIRE) — Vor Bio (Nasdaq: VOR), a clinical-stage cell and genome engineering company, today announced initial clinical data from VBP101, its Phase 1/2a multicenter, open-label, first-in-human study of tremtelectogene empogeditemcel or “trem-cel” (formerly VOR33) in patients with acute myeloid leukemia (AML). The data observed from the first treated patient support the potential of a trem-cel transplant to be successfully manufactured, to engraft normally, and to maintain blood counts following treatment with the CD33-targeted therapy Mylotarg. The clinical trial continues to enroll patients and additional data are expected in 2023.

“These early engraftment data represent the first time genome engineering has been used to genetically alter donor cells by removing an antigen present on blood cells, thereby allowing treatment using a CD33 targeted therapy while protecting normal blood cells,” said Dr. Robert Ang, Vor Bio’s President and Chief Executive Officer. “These encouraging data represent the first clinical validation of our platform to potentially enable next-generation transplants for patients with blood cancers. We look forward to sharing additional data updates in 2023.”

Trem-cel Displayed Normal Engraftment

A product dose of 7.6 x10⁶ CD34⁺ viable cells/kg, with a CD33 editing efficiency of 88% was manufactured.

Following myeloablative conditioning, trem-cel was infused with no infusion reactions. The patient achieved neutrophil engraftment 10 days post-transplant which was within expectations for CD34-enriched transplants. Platelet recovery was observed on Day 22. Hematopoietic cell sub-population reconstitution was robust with over 90% of peripheral blood cells negative for CD33 expression, and 100% donor chimerism was achieved. These data provide proof-of-concept that trem-cel can engraft as expected and that CD33 does not appear to be biologically necessary for engraftment and hematopoietic reconstitution.

Mylotarg Tolerated at Initial Dose Level

The patient received Mylotarg at a dose of 0.5 mg/m². At this dose, Mylotarg saturates CD33 antigen in patients with relapsed/refractory AML¹, and in the original Phase 1 trial of Mylotarg², neutropenia was observed across dose levels starting at 0.25mg/m² within 14 days of infusion. No treatment related adverse events and no liver enzyme changes were observed through day 20 following Mylotarg dosing. No negative impacts to neutrophil and platelet counts were observed through day 20, suggesting tolerability at this initial dose level.

“The unmet medical need for AML is significant and hematopoietic cell transplant is the best hope for these patients,” said Brenda Cooper, M.D., Professor of Medicine in the Cellar Therapy Program at University Hospitals, Seidman Cancer Center, and an investigator in the VBP101 study. “Early treatment data in the first patient show that trem-cel can engraft normally and maintain normal hematopoiesis following Mylotarg dosing, which typically causes severe cytopenias. These data support the promise of this approach.”

¹  Mylotarg ODAC 2017

²  Sievers 1999 Blood 93:3678

Conference Call & Webcast Information

Members of the Vor Bio management team, joined by Dr. Brenda Cooper, will conduct a live conference call and webcast today at 8:00 am Eastern Time.

Listeners can register for the webcast via this link.

Analysts wishing to participate in the Q&A session should use this link.

A replay of the webcast will be available via the investor section of the Company’s website at www.vorbio.com approximately two hours after the call’s conclusion.

About AML

AML is the most common type of acute leukemia in adults and one of the deadliest and most aggressive blood cancers, affecting 20,000 newly diagnosed patients each year in the United States. Approximately half of patients with AML who receive a hematopoietic cell transplant (HCT) suffer a relapse of their leukemia, with two-year survival rates of less than 20%, and relapse rates are higher for patients with certain adverse risk features. The fragility of engrafted hematopoietic stem cells prevents treatment following transplant, giving the cancer a chance to return.

About the VBP101 Clinical Trial

VBP101 is a Phase 1/2a, multicenter, open-label, first-in-human study of trem-cel in participants with AML who are undergoing human leukocyte antigen (HLA)-matched allogeneic hematopoietic cell transplant (HCT). Trem-cel is an allogeneic CRISPR/Cas9 genome-edited hematopoietic stem and progenitor cell (HSPC) therapy product, lacking the CD33 protein. It is being investigated for participants with CD33⁺ AML at high risk for relapse after HCT to allow post-HCT targeting of residual CD33⁺ acute AML cells using Mylotarg without toxicity to engrafted cells. Participants undergo a myeloablative HCT with matched related or unrelated donor CD34-selected HSPCs engineered to remove CD33 expression (trem-cel drug product). Mylotarg is given after engraftment for up to four cycles. The primary endpoint is the incidence of successful engraftment, defined as the first day of 3 consecutive days of absolute neutrophil count (ANC) ≥500 cells/mm² by day 28. Part 1 of this study is evaluating the safety of escalating Mylotarg dose levels to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose. Part 2 will expand the number of participants to evaluate the Mylotarg recommended Phase 2 dose. For more information, visit: https://clinicaltrials.gov/ct2/show/NCT04849910

About Trem-cel

Tremtelectogene empogeditemcel (trem-cel), formerly VOR33, is a genome-edited hematopoietic stem and progenitor allogeneic donor product candidate where CD33 has been deleted using genome engineering. Transplant with trem-cel is designed to replace standard of care transplants for patients suffering from AML and potentially other blood cancers. Trem-cel has the potential to enable powerful targeted therapies in the post-transplant setting including CD33-targeted CAR-T cells.

About Vor Bio

Vor Bio is a clinical-stage cell and genome engineering company that aims to change the standard of care for patients with blood cancers by engineering hematopoietic stem cells to enable targeted therapies post-transplant. For more information, visit: www.vorbio.com.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. The words “aim,” “anticipate,” “can,” “continue,” “could,” “design,” “enable,” “expect,” “initiate,” “intend,” “may,” “on-track,” “ongoing,” “plan,” “potential,” “should,” “target,” “update,” “will,” “would,” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Forward-looking statements in this press release include Vor Bio’s statements regarding the feasibility of a trem-cel transplant to be successfully manufactured, to engraft normally, to maintain blood counts following treatment with Mylotarg following allogeneic hematopoietic cell transplant and to be well tolerated, the potential of Vor Bio’s platform, and timing expectations for additional release of clinical data. Vor Bio may not actually achieve the plans, intentions, or expectations disclosed in these forward-looking statements, and you should not place undue reliance on these forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in these forward-looking statements as a result of various factors, including: uncertainties inherent in the initiation and completion of preclinical studies and clinical trials and clinical development of Vor Bio’s product candidates; availability and timing of results from preclinical studies and clinical trials; whether interim results from a clinical trial will be predictive of the final results of the trial or the results of future trials; expectations for regulatory approvals to conduct trials or to market products; the success of Vor Bio’s in-house manufacturing capabilities and efforts; and availability of funding sufficient for its foreseeable and unforeseeable operating expenses and capital expenditure requirements. The interim data presented in this press release is based on one patient and future results for this patient or additional patients may not produce the same or consistent results. These and other risks are described in greater detail under the caption “Risk Factors” included in Vor Bio’s most recent annual or quarterly report and in other reports it has filed or may file with the Securities and Exchange Commission. Any forward-looking statements contained in this press release speak only as of the date hereof, and Vor Bio expressly disclaims any obligation to update any forward-looking statements, whether because of new information, future events or otherwise, except as may be required by law.

Contact:

Investors & Media

Sarah Spencer

+1 857-242-6076

sspencer@vorbio.com

EX-99.2

Exhibit 99.2

VBP101 Clinical Update December 7, 2022

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”) that involve substantial risks and uncertainties. All statements, other than statements of historical facts, contained in this Presentation, “plan,” “potential,” are forward “project,” looking “should,” statements “target,” including, “vision,” “will,” but not “would,” limited or to, other terms similar such expressions. as “anticipate,” Such “believe,” forward-looking “continue,” statements “could,” “estimate,” in this Presentation “expect,” “intend,” include those “may,” regarding Vor Bio may Vor not Bio’s actually plans, achieve strategies the and plans, expectations intentions, for or expectations its preclinical disclosed and clinical in these programs, forward-looking including the statements. anticipated These milestones forward-looking and related statements catalysts of should such not programs. be relied upon to, Vor as Bio’s representing dependence Vor on Bio’s its views product as candidates of any date VOR33 subsequent (trem-cel) to the and date VCAR33 of this Presentation. ALLO, the risks Factors inherent that in biopharmaceutical could cause actual product results development to differ include, and but clinical are not trials, limited including clinical trials the will lengthy validate and the uncertain safety and regulatory efficacy approval of VOR33 process, (trem-cel) uncertainties and VCAR33 related programs to the timing in acute of initiation, myeloid leukemia enrollment or and other completion indications, of and clinical the trials, impact whether of the COVID-19 the pandemic change. These on Vor results Bio’s may business, not be operations, reproduced strategy in subsequent and anticipated patients. milestones, These and among other risks others. are described The first patient in greater data detail presented under herein the caption is preliminary “Risk Factors” and is in subject Vor Bio’s to reports plans, intentions filed with or the expectations Securities and disclosed Exchange in our Commission forward-looking (“SEC”), statements, and in other and filings you should that Vor not may place make undue with reliance the SEC on in our the forward-looking future. We may statements. not actually Actual achieve results the or included events could in this differ Presentation materially represent from the plans, our views intentions as of the and date expectations of this Presentation. disclosed in We the anticipate forward-looking that subsequent statements events we make. and developments In addition, the will forward-looking cause our views statements to change. otherwise. 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 Certain information contained in this Presentation relates to or is based on studies, publications, surveys and other data obtained from third party sources and Vor Bio’s own internal representation estimates as to and the research. adequacy, While fairness, we believe accuracy these or third-party completeness sources of any to information be reliable as obtained of the date from of third this party Presentation, sources. In it has addition, not independently the third party verified, information and makes included no in we this believe Presentation our own may internal involve research a number is reliable, of assumptions such research and limitations, has not been and verified there can by any be no independent guarantee source. as to the accuracy or reliability of such assumptions. Finally, while VCAR33AUTO and NMDP-Sponsored Trial. A T cell therapy using the same chimeric antigen receptor construct as VCAR33ALLO is being studied in a Phase 1/2 clinical trial sponsor sponsored of this by the trial, National the NMDP Marrow has Donor permitted Program us to cross-reference (“NMDP”), and timing its IND of for data this release trial in is future dependent IND applications on the investigators that we may conducting submit with the the trial. FDA. Although For more we are information not the regarding of results that the NMDP may be trial, observed see “Risk in clinical Factors trials” – We in have our Annual not successfully Report on tested Form 10-K our product for the year candidates ended in December clinical trials 31, 2021 and any filed favorable with the SEC preclinical and such results other are filings not predictive that we may make with the SEC from time to time. 2

Today’s Agenda Agenda Speaker Agenda Speaker Robert Ang, MBBS, MBA, President & CEO, Vor Bio Introductory Remarks Siddhartha Mukherjee, MD, DPhil, Founder of Vor Bio Overview of VBP101 Eyal Attar, MD, Chief Medical Officer, Vor Bio VBP101 Clinical Trial Results Brenda Cooper, MD, Professor of Medicine & Investigator, VBP101 Study Vor Bio Platform Tirtha Chakraborty, PhD, Chief Scientific Officer, Vor Bio Closing Remarks Robert Ang, MBBS, MBA, President & CEO, Vor Bio Q&A 3

Our Founding Siddhartha Mukherjee, MD, DPhil, Founder of Vor Bio

A Radically Protect the Healthy Cells, Simplistic Idea Expose the Cancer 5

From Vision To Reality Scale Infrastructure Expertise 6

Vor Bio’s Vision Robert Ang, MBBS, MBA, President & CEO, Vor Bio

Changing the Thinking on Tumor Targeting Traditional Paradigm Vor Bio Paradigm: Problem for Drug Development Engineered HSCs (eHSCs) Cancer Healthy Cancer cell cell cell Few unique cancer antigens, so Remove target expression Target cancer antigens drugs kill both cancer and healthy on healthy cells so that killing to kill cancer cells cells through on-target toxicity is cancer-specific 8

Can We Establish a New Standard of Care for AML? AML Journey Induction, Watchful waiting Relapse Consolidation Diagnosis Transplant • Ideal treatment window • Few effective • However, fragile marrow treatment options Opportunity: • 2-year survival is <20% eatment-resistant ansplant enabling post-transplant therapy 9

Key Questions To Create Protected eHSC Transplants Do biologically Can eHSCs be dispensable produced at scale, targets exist? in time, and with quality? Will eHSC transplants engraft and function normally? Can eHSCs enable safe dosing of heme-toxic therapies? 10

Overview of VBP101 Eyal Attar, MD, Chief Medical Officer, Vor Bio

Goals for Our First eHSC in Patients With AML 1 Manufacturing Streamlined process with high editing efficiency 2 Engraftment Successful timely neutrophil engraftment, platelet recovery 3 Reconstitution Repopulate blood system and fully functional cells 4 Safety Disease status and AEs consistent with traditional HCTs 5 Protection Reduce on-target heme toxicity from Mylotarg 13

VBP101 Clinical Trial Results Brenda Cooper, MD, Professor of Medicine & Investigator, VBP101 Study

AML Background • AML is a fatal disease with poor outcomes Post-Transplant Overall Survival • Patients with high-risk disease are referred for allogeneic hematopoietic cell transplantation (HCT) • Approximately 40-50% of AML patients have MRD+ or residual disease at the time of HCT • Outcomes for these patients are particularly poor • Relapse rate is considerable even in patients without detectable MRD Araki et al (2016) JCO 34:329 16

Transplant Outcomes • AML relapse is the leading cause of death after HCT There are no approved post-HCT maintenance Post-Transplant Relapse • therapies • Targeted treatments are generally confined to small subgroups of patients • For patients who relapse post-HCT, treatments are limited and poorly tolerated due in large part to myelosuppression • Treatments that address the majority of AML are desperately needed Araki et al (2016) JCO 34:329 17

CD33, Mylotarg, and Trem-cel • CD33 expressed on most AML and on normal hematopoietic cells • alone Mylotarg or in (gemtuzumab combination ozogamicin), with chemotherapy is an anti for -CD33 favorable ADC approved risk patients, in front and for line R/R AML AML • Could setting potentially be used post-HCT to prevent or treat relapse in the post-HCT • Use is limited in large part due to myelosuppression • editing Trem-cel technology is an allogeneic donor stem cell graft where CD33 is deleted using CRISPR gene • CD33 shown to be dispensable for normal hematopoiesis in animal models • CD33 Trem- cel CAR is -T hypothesized cells, that target to enable AML cells use of while CD33 sparing -directed normal therapies, blood cells such as Mylotarg or 18

Patient 1 Characteristics and High-Risk AML Features Characteristic High Risk AML Feature • 64-yo female with complex karyotype AML with MDS-related changes Age >60 • Required 2 courses of cytarabine and daunorubicin to achieve clinical CR Primary induction failure Remission Status (but MRD positive) Relapsed AML AML Type AML with MDS changes • 3 cycles high-dose cytarabine consolidation Karyotype: Adverse 41-44, X, -X[17] ,add (3) (p22) [2] , Disease relapsed with 5-10% blasts cytogenetics inv (3) (p25q21) [10] ,-5[19] ,+6 [5] • ,der(8;17) (q10; q10), add(9) (q22), -11,add(12) (p11.2) [15] ,add (12) • Referred for allogeneic HCT due to high risk factors (p11.2) [5],-17[14] ,-18 [9], -19[11], add (19) (q13.3) [5] ,-22,+3-4 mar agent, achieved [cp20] • Received 2 cycles of venetoclax + hypomethylating remission with MRD+ (1.8% by flow cytometry) Molecular Features Mutant DNMT3A, KDM6A, TP53 Incomplete CR with MRD positive • 10/10 matched unrelated donor identified CR2 Status status by flow (1.8%) 19

Protocol Treatment and Early Post-HCT Clinical Course • Enrolled on VBP101 to receive trem-cel Trem-cel Drug Product Characteristics • Sufficient PBSCs collected after GCSF and plerixafor mobilization Trem-cel CD34+ dose 7.6 x 106 cells/kg for trem-cel manufacturing and backup graft Total CD34+ cells in drug 544.5 x 106 cells product Total CD3 in drug product <0.6 x 105 cells/kg • D -9 to -1: Busulfan/fludarabine/melphalan/rATG • Tolerated well, no GVHD prophylaxis used with CD33 gene editing efficiency 88% this type of HCT • D0: Trem-cel infused: no related reactions or AEs • Standard supportive care given: prophylactic anti-microbials and blood product support • Day +10: Neutrophil engraftment (1st of 3 consecutive days with ANC?500) • Day +15: Last platelet transfusion administered, discharged from hospital 20

Peripheral Blood Neutrophil Engraftment Day 10 and Platelet Recovery Day 22 Median engraftment* Trem-cel Neutrophil Engraftment Pt was transfused platelets at a threshold of 30k/µL *CTN 1301 trial (median for CD34 selected graft), Luznik 2021 JCO 40:356 21 due to prior subdural hematoma

Select Adverse Events Reported Post Trem-cel Infusion Serious Adverse Events Grade Date Noted Comments Renal colic 3 D+50 Attributed to passed kidney stone Deep venous thrombosis 3 D+50 Resolving All Infections Grade Date Noted Comments Skin infection 2 D+21 Resolved Skin infection 1 D+37 Ongoing CMV reactivation 2 D+31 Resolving BK virus (urine) 2 D+50 Asymptomatic Hepatic AE Grade Date Noted Comments LFT elevation (AST/ALT) 2 D+36/+39 Both attributed to anti-fungal therapy, 1 D+56/+56 resolved after discontinuation No trem-cel related events reported 22 Data cutoff: Day 87

Patient 1: CD33 expression, counts, and chimerism at day 28 and 60 assessments CD33 Negative Cells, % Day 28 Day 60 Blood Counts Day 28 Day 60 PB neutrophils 95 96 White blood cells (x1000/ìL) 3.9 3.4 PB monocytes 94 94 Hemoglobin (g/dL) 7.7 10 BM maturing myeloid 95 93 Platelets (x1000/ìL) 103 120 BM maturing monocytes 92 90 Absolute neutrophils/ìL 2300 2770 BM CD34+ 94 91 Absolute lymphocytes/ìL 510 180 PB: Peripheral Blood BM: Bone Marrow Lineage, % Donor Chimerism Day 28 Day 60 Whole blood 100 100 Myeloid 100 100 NK 100 100 T lymphoid QNS QNS B lymphoid QNS 100 QNS: Quantity Not Sufficient 23 For standard CD34-selected transplants, limited T/B lymphoid recovery expected through D+60

Historic Experience Following Single Dose Mylotarg CD33 Saturation Following Mylotarg Single Dose Reference: Mylotarg Phase 1 Study 100 Observed Neutropenia 80 >1,500 <200 (%) 60 cells/ìL cells/ìL Saturation 40 n=8 out of 9 Occurred within 14 days of infusion 20 regardless of study dose from 0 0.25 to 9 mg/m2 0.25 0.5 1 2 4 5 6 7.5 9 Mylotarg Dose (mg/m2) Sievers 1999 Blood 93:3678 Mylotarg ODAC 2017 24

Blood counts and LFTs following first Mylotarg administration Transplant Day D28 D60 D68 D73 D76 D84 D87 Mylotarg Day D1 D6 D9 D17 D20 Abs Neutrophils/ìL 2,300 2,770 2,260 3,140 3,490 3,330 3,250 Plt (x1000/ìL) 103 120 91 118 120 110 94 ALT (IU/L) 6 78 32 14 14 12 12 AST (IU/L) 17 49 15 14 15 15 15 Mylotarg dose No reported Mylotarg-related adverse events through Cycle 1, D20 (0.5 mg/m2) 25

Conclusions • First HCT of a patient with high risk, relapsed AML using trem-cel, a CD33-deleted allogeneic donor graft • Uneventful post-HCT course • Engraftment occurred rapidly and appears comparable to unedited cells • No unexpected post-HCT AEs • High percentage (>90%) sustained CD33-negative hematopoiesis • No cytopenias observed through Cycle 1, D20 following Mylotarg 0.5 mg/m2 dosing • Data suggest trem-cel may enable post-HCT Mylotarg and other CD33-directed therapies 26

Vor Bio Platform Tirtha Chakraborty, PhD, Chief Scientific Officer, Vor Bio

Vor Bio’s Novel Technology Platform Hematopoietic Genome CAR-T Stem Cells Engineering • Deletion of biologically- • Cas9, Cas ortholog • Allogeneic, healthy donor redundant targets enzymes, base editing cell source • Doing no harm to HSC • Single and multiplex • Single targets and function editing dual-specific CARs 28

Hematopoietic HSC Biology Platform Stem Cells Refine HSC identification and pre-clinical transplant modelling HSC Identity Transplant PoC Identified LT HSCs Retention of Stemness Primary Secondary 16 weeks 12 weeks 100 80 (%) 60 Frequency of True HSC Frequency in 40 Groups CD34s vivo Chimersim Bulk CD34+ 93.9%—20 CD34+ CD90+ Stem/Prog 14.6% 1 out of 6715 0 mPB CB 10x CD49f+ HSCs 2.22% 1 out of 2117 Primary Secondary “New panel” HSCs 0.18% 1 out of 210 29

CAR-T CAR-T Platform Multi-valent CAR and process improvement for drug product enrichment Multi-valent CAR Process enrichment 100 Input (Pre-Enrichment) Elution (Purified) 80 Cells 60 Viable 24.3% 94.4% of 40 % H SSC—20 SSC 0 CAR (protein L) UTD T Tandem UTD T Tandem UTD T Tandem UTD T Tandem HL-60WT HL-60CD33KO HL-60CLL-1KO HL-60DKO 31

Closing Remarks Robert Ang, MBBS, MBA, President & CEO, Vor Bio

Trem-cel: First Patient Data Observations To Date What Is Next? 1 Manufacturing Robust process • Confirmation of findings with Normal engraftment, 2 Engraftment additional patients complete chimerism • Test protection robustness with Normal CD33-negative repeat Mylotarg dosing and dose 3 Reconstitution myeloid development escalation • Potentially broaden eligibility No related SAEs or 4 Safety evidence of GvHD ALLO • VCAR33 : IND 1H 2023 • Trem-cel/VCAR33 Treatment System 5 Protection Tolerable at this dose 33

Q&A

www.vorbio.com

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