Intellia Therapeutics, Inc. · NASDAQ:NTLA

Intellia Therapeutics — Technical Presentation (December 2020)

11 slides from Intellia Therapeutics's technical presentation, Dec 5, 2020

  1. Slide 1: NTLA-5001, a T Cell Product Candidate with CRISPR-Based Targeted Insertion of a WT1-Specific TCR

    #1435 NTLA-5001, a T Cell Product Candidate with CRISPR-Based Targeted Insertion of a High-Avidity, Natural, WT1-Specific TCR, Shows Efficacy in In Vivo Models of AML and ALL Ruggiero E.1, Liu D.2, Prodeus A.2, Becker A.2, Foisey M.2, Balwani I.2, Dutta I.2, Zhang, Q.2, Arredouani M.S.2, McKee M.3,

  2. Slide 2: Conflict of Interest Disclosure and Legal Disclaimer

    Conflict of Interest Disclosure and Legal Disclaimer • D. Liu, A. Prodeus, A. Becker, M. Foisey, I. Balwani, I. Dutta, Q. Zhang, M.S. Arredouani, M. McKee, L. Sepp-Lorenzino, and B.C. Schultes are employees of Intellia Therapeutics, Inc. • F. Ciceri and C. Bonini are consultants for Intellia Therape

  3. Slide 3: NTLA-5001: Engineered T Cell Product Candidate with Site-Specific Insertion of a High-Avidity, Natural TCR

    NTLA-5001: Engineered T Cell Product Candidate with Site- Specific Insertion of a High-Avidity, Natural TCR to WT137-45 • Initial clinical indication: AML, the most common type of acute leukemia in adults with limited treatment options1 • HD1-TCR selected for NTLA-5001 based on high avidity and abil

  4. Slide 4: CRISPR Editing Overcomes Key Challenges in TCR T Cell Engineering

    CRISPR Editing Overcomes Key Challenges in TCR T Cell Engineering Traditional tgTCR addition TRAC Insertion only Heterogenous Cell Product Endogenous TCR β chain still present Non-edited T cells with Key Challenges T cells inserted TCR T cells with mixed TCRβ chains • Mutagenesis risk from random le

  5. Slide 5: Proprietary Sequential Editing Process Enables Multiple Edits with High Efficiency and Cell Viability

    Proprietary Sequential Editing Process Enables Multiple Edits with High Efficiency and Cell Viability Cell Engineering Workflow T Cell Editing T Cell Expansion Endogenous % WT1 TCR DAY 0 150 TCR KO Insertion % WT1 TCR insertion (CD3+Vb8+) Thaw 80 Day 10 Day 14 % Engodenous TCR (CD3+Vb8-) 100 p=0.07

  6. Slide 6: WT1-TCR T Cells Engineered with Proprietary Process Have Enhanced Potency vs. Standard Methods

    WT1-TCR T Cells Engineered with Proprietary Process Have Enhanced Potency vs. Standard Methods T Cell Memory Phenotype IFN-γ Secretion Re-stimulation Stress Test Standard Process Proprietary Process K562-HLA-A*02:01+ Cells OCI-AML3 pulsed cells 6000 Standard 150 OCI-AML3+Peptide Proprietary - Proces

  7. Slide 7: Proprietary Process Minimizes Translocations and Gene Expression Changes vs. Standard Electroporation Process

    Proprietary Process Minimizes Translocations and Gene Expression Changes vs. Standard Electroporation Process KromaTiD dGHTM Assay Shows Gene Expression Profiling1 No Detectable Translocations With Sequential Editing (780 genes) 15 Translocations to other chromosomes Unedited Standard Proprietary Re

  8. Slide 8: WT1-Specific TCR T Cells Are Efficacious In Vivo in Mice; Proprietary Process Enhances Anti-Tumor Activity

    WT1-Specific TCR T Cells Are Efficacious In Vivo in Mice; Proprietary Process Enhances Anti-Tumor Activity AML AML in Bone Marrow (Day 54, End of Study) 100 ** %AML Cells/Living Cells 80 **** 60 40 **** 20 0 AML Monitoring in Blood AML in Spleen (Day 54, End of Study) 500 pAML Alone 100 400 MART1-TC

  9. Slide 9: WT1-Specific TCR T Cells Are Efficacious In Vivo in Mice; Human IL2/IL15 Enhances Anti-Tumor Activity

    WT1-Specific TCR T Cells Are Efficacious In Vivo in Mice; Human IL2/IL15 Enhances Anti-Tumor Activity ALL 10000 T Cells in Bone Marrow (Day 27) Live CD45+ CD3+ Vb8+/- CD8+ cells/ul NOG 1000 NOG-hIL15 NOG-hIL2 100 10 1 Tumor Progression in 697 ALL Model 0.1 N/A NOG 10 11 NOG-hIL15 TCR KO T cells with

  10. Slide 10: Conclusions and Next Steps for NTLA-5001

    Conclusions and Next Steps for NTLA-5001 • Proprietary process enables efficient, scalable genome editing – ~99% KO efficiency of target genes; 50-70% in locus insertion of tgTCRs – Sequential editing with high viability and potential for safer products – Faster T cell expansion with favorable T cel

  11. Slide 11: Intezia Therapeutics

    Intezia THERAPEUTICS

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