Slide 1: VBP101 Clinical Update
VBP101 Clinical Update December 7, 2022
Slide 2: Disclaimer
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 s
Slide 3: Today's Agenda
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 Medici
Slide 4: Our Founding
Our Founding Siddhartha Mukherjee, MD, DPhil, Founder of Vor Bio
Slide 5: A Radically Simplistic Idea: Protect the Healthy Cells, Expose the Cancer
A Radically Protect the Healthy Cells, Simplistic Idea Expose the Cancer 5
Slide 6: From Vision To Reality
From Vision To Reality Scale Infrastructure Expertise 6
Slide 7: Vor Bio's Vision
Vor Bio’s Vision Robert Ang, MBBS, MBA, President & CEO, Vor Bio
Slide 8: Changing the Thinking on Tumor Targeting
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
Slide 9: Can We Establish a New Standard of Care for AML?
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-tra
Slide 10: Key Questions To Create Protected eHSC Transplants
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
Slide 11: Overview of VBP101
Overview of VBP101 Eyal Attar, MD, Chief Medical Officer, Vor Bio
Slide 12: VBP101: Trem-cel (VOR33) + Mylotarg Phase 1/2a Clinical Trial
LV J VBP101: Trem-cel (VOR33) + Mylotarg Phase 1/2a Clinical Trial Transplant Day 28. Anti-CD33. Infusion Engraftm Therapy 7 — fy —— 1 —1) (EI — key Endpoints — @ remcet errant @ woe potion @ retort sr Clinical Tal Sites © skcc (ny) © UC San Diego Cancer Ctr. (CA) © The National Cancer institute (MD
Slide 13: Goals for Our First eHSC in Patients With AML
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
Slide 14: Trem-cel Manufacturing and Specifications for Patient
LV J Trem-cel Manufacturing and Specifications for Patient 1 Apheresis Material Cell Genome Harvest Release preparation selection engineering testing lida Characteristics Release Criteria Pt #1 Drug Product Product dose (viable CD34* cells) 23x 10° collsikg 7.6 x 10° cellsikg Gene editing efficiency
Slide 15: VBP101 Clinical Trial Results
VBP101 Clinical Trial Results Brenda Cooper, MD, Professor of Medicine & Investigator, VBP101 Study
Slide 16: AML Background
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 th
Slide 17: Transplant Outcomes
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
Slide 18: CD33, Mylotarg, and Trem-cel
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 p
Slide 19: Patient Characteristics and High-Risk AML Features
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
Slide 20: Protocol Treatment and Early Post-HCT Clinical Course
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+ cell
Slide 21: Peripheral Blood Neutrophil Engraftment Day and Platelet Recovery Day
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
Slide 22: Select Adverse Events Reported Post Trem-cel Infusion
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 CM
Slide 23: Patient 1: CD33 expression, counts, and chimerism
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
Slide 24: Historic Experience Following Single Dose Mylotarg
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
Slide 25: Blood counts and LFTs following first Mylotarg administration
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
Slide 26: Conclusions
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 h
Slide 27: Vor Bio Platform
Vor Bio Platform Tirtha Chakraborty, PhD, Chief Scientific Officer, Vor Bio
Slide 28: Vor Bio's Novel Technology Platform
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 d
Slide 29: Hematopoietic Stem Cells Platform: HSC Biology
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
Slide 30: Genome Engineering Platform
LV J Genome Engineering Platform DO Eas Multiplex HSC KO and reduced translocation ‘Sequential Cas9 Editing Base Editing Transactional Rate 5 I | By a cose comes 8 Doub KO ‘ove KO Smauronis —Sapantst Seq Bose ee a) Con vom cosinor ting Lo cus ‘Genome Engineering Strategy Vor
Slide 31: CAR-T Platform
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-60W
Slide 32: Closing Remarks
Closing Remarks Robert Ang, MBBS, MBA, President & CEO, Vor Bio
Slide 33: Trem-cel: First Patient Data Observations To Date and What Is Next
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 Reconstitut
Slide 34: Q&A
Q&A
Slide 35: www.vorbio.com
www.vorbio.com