Vor Biopharma Inc. · NASDAQ:VOR
Vor Biopharma — Technical Presentation (December 2023)
19 slides from Vor Biopharma's technical presentation, December 2023
Slide 1: Multimodal atlas of paired diagnosis and relapse AML samples
Multimodal atlas of paired diagnosis vy and relapse AML samples enables W novel therapeutic targeting of < surface antigens b | wy Matthew H. Ung, PhD a, Associate Director, Quantitative Biology Vor Bio, Cambridge MA, USA 7 Confidential
Slide 2: We use genome engineering to make healthy cells invisible to drugs
We use genome engineering to make healthy cells invisible to drugs Vor Paradigm: Engineered HSCs (eHSCs) Few unique cancer antigens, so Remove target expression drugs kill both cancer and healthy on healthy cells so that killing cells through on-target toxicity is cancer-specific Confidential
Slide 3: Patient to patient heterogeneity presents obstacles to treatment
Patient to patient heterogeneity presents obstacles to treatment Heterogeneity =e =e =e =e =e Confidential
Slide 4: Evolution of leukemic blasts presents obstacles to treatment
Evolution of leukemic blasts presents obstacles to treatment Heterogeneity =e =e =e =e =e x ow s & . xX & R oO) es we ye Or <& xe ee Confidential
Slide 5: University Health Network matched AML samples
University Health Neon a Clinical metadata ¥ Treatment history v Sex vY FAB subtype ¥ Cytogenetics ¥ Mutation information ¥ Vital status Y Survival information ¥ Time to relapse 56 matched AML bone marrow samples Confidential
Slide 6: Myeloid markers expressed at targetable levels at diagnosis and relapse
% Antigen* on AML Blasts 4 myeloid markers are expressed at targetable levels at diagnosis and relapse Flow cytometry CD33 CLL-1 CD123 EMR2 1005 o> GH Ke 2 Julia Etchin 80-4 im 60-4 C) 40-4 20-4 Julia DiFazio Yonina Keschner D = Diagnosis R = Relapse Confidential
Slide 7: Myeloid markers expressed at targetable levels at diagnosis and relapse
4 myeloid markers are expressed at targetable levels at diagnosis and relapse Flow cytometry with QuantiBRITE CD33 CLL-1 CD123 EMR2 Flow cytometry CD33 CLL-1 CD123 EMR2 1005 o> GS oH 100000" Z x 0 ® < m 8 =| = 2 P 5 100004 a | 5 3 % 40-4 g 7) o 1000-4 ob — S oo s z = 3 4 3 0 T T T T T * 100 9 €9 HF]
Slide 8: Single cell RNA sequencing of matched AML samples with feature barcoding
Single cell RNA sequencing of matched AML samples with feature barcoding of 81 surface antigens AML Antigens Surface Antigens Heme Tissue Antigens Mass Spectrometry The Cancer Exclusion of Protein Discovery in /6161| Surfaceome Atlas |538| non-Heme Tissue 200 Patient Samples —>| — Antigens ene eee e
Slide 9: Multimodal atlas of AML reveals distinct cell populations
Multimodal atlas of AML reveals distinct cell populations CLL-1 400,000 cells Surface antigen expression Confidential
Slide 10: Multimodal atlas of AML reveals distinct cell populations
Multimodal atlas of AML reveals distinct cell populations Colored by patient oe 400,000 cells @ Diagnosis © Relapse ae Confidential
Slide 11: Cell surface antigen density can be estimated for each blast
11 Cell surface antigen density can be estimated for each blast by incorporating QuantiBRITE information o Feature Ed barcoding = Antigen ® ADT © 10,000 e@ CD33 oO a 2 e CLL-1 3 e@ CD123 a e EMR2 $ 1,000 ae 3 Timepoint & @ Diagnosis 2 4 Relapse © oO Zz 100; ABC. 0.0 05 10 15 20 25 30 35 QuantiBRITE
Slide 12: Estimated blast surface antigen density reveals targetable antigens
Estimated blast surface antigen density reveals targetable antigens across patients at diagnosis and relapse Diagnosis iat 2 z = % || Mies 1 ILIRAP CD45RA 17687 *2000 antigens corresponds to a normalized ADT value of 1.8 a "I Passes | | tee | icD44 cbs ||cp30s — lL icpi1a # estimated antigens/blast
Slide 13: Estimated blast surface antigen density reveals targetable antigens
13 Estimated blast surface antigen density reveals targetable antigens across patients at diagnosis and relapse ae i Diagnosis mt aM er Lh | if | i (ft WI eo bis i T lt TT ee Te TTT a i Lie | ‘i i= Relapse | ee HLA-DR cps4 CD99 D805 cD11A CLL-1 can make up for low CD33 cpa Ma .--8 mM nc — Pt i 4 cps
Slide 14: Estimated blast surface antigen density reveals targetable antigens
Estimated blast surface antigen density reveals targetable antigens across patients at diagnosis and relapse Dia Relapse RO Ki , es || ee # estimated a it =p be IL ‘2 | coe e000 at i 1"! ‘aR = I< CD47 Hi i wih l i i, 4 H e---p0117 ° lif) | 0 am | 1 CTA CD33 Patient - (a | | i i a il pp4eD Pationt_26
Slide 15: Multi-targeting strategies can leverage antigen combinations
Multi-targeting strategies can leverage antigen combinations: Example from a single patient sample Coverage [Ml Co-expressed [) CD33 = CLL~1 100 — OR gated CAR T fox] = : TT Pearson r B0 1 I : across blasts 70 1 | ie G ° & 5S 50 -0.5 . . i © 40 3s i 30 aa ° Mm % | ey, 10 Y on Ks 9 eg o. © £ © € © S
Slide 16: CD33 expression is higher in relapse blasts: another patient
CD33 expression is higher in relapse blasts: Example from another patient ES . : os Diagnosis Low CD33 cose antigen expression 9 5 IL1RAP | CD45RA IT6B7 16 Relapse HLA-DR cps4 CD99 D305 cD11A cpa7 cps2 p17 CD33 cp49D cut cpas cp7 D205 cp244 cp123 cov aB7 EMR2 CD45RA # estimated antigens/blast Confid
Slide 17: CD33 upregulation associated with proliferation and downregulated inflammation
CD33 upregulation on cell surface is associated with proliferation and downregulation of cell-intrinsic inflammation in the patient " & Cell cycle phase Ms Mics RNA expression Patient 26 blasts 50 2 Q 8 g ct 2 25 3 Pp 5 a 3 x mar ae » [imeem 0 B Differentially expressed genes (logs fold change > 2)
Slide 18: Summary
Summary ¥Vor’s AML atlas enables extensive characterization of inter- and intra- patient blast heterogeneity ¥ CD33 and CLL-1 are among the highest expressed antigens across entire cohort ¥ Transcriptomic analysis of a single patient identified downregulation of inflammatory pathways in CD33-high re
Slide 19: Acknowledgement
19 Acknowledgement Toronto General Toronto Western Princess Margaret 1S Toronto Reha Michener Institute University Health Network Andrea Arruda Mark Minden The patients and their families and caregivers Confidential
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