EX-99.2 3 d431519dex992.htm EX-99.2 EX-99.2

Exhibit 99.2

 

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VBP101 Clinical Update December 7, 2022


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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


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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


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


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


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From Vision To Reality Scale Infrastructure Expertise 6


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


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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


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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


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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


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


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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


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


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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


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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


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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


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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


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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


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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


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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


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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


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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


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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


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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


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


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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


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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


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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


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


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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


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Q&A


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www.vorbio.com