Intellia Therapeutics, Inc. · NASDAQ:NTLA

Intellia Therapeutics — American Society of Gene and Cell Therapy 22nd Annual Meeting (April 2019)

15 slides from Intellia Therapeutics's conference presentation, Apr 29, 2019

  1. Slide 1: CRISPR/Cas9-Mediated Targeted Insertion of Human F9 Achieves Therapeutic Circulating Protein Levels in Mice and Non-Human Primates

    CRISPR/Cas9-Mediated Targeted Insertion of Human F9 Achieves Therapeutic Circulating Protein Levels in Mice and Non-Human Primates Hon-Ren Huang, Ph.D. American Society of Gene and Cell Therapy 22nd Annual Meeting April 29, 2019 1 Disclosure: Employee of Intellia Therapeutics, Inc.

  2. Slide 2: Intellia Therapeutics' Legal Disclaimer

    Intellia Therapeutics’ Legal Disclaimer This presentation contains “forward-looking statements” of Intellia Therapeutics, Inc. (“Intellia”) within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements include, but are not limited to, express or implied

  3. Slide 3: Intellia's Modular Non-Viral Delivery of CRISPR/Cas9 Addresses Disease at the Genetic Level

    Intellia's Modular Non-Viral Delivery of CRISPR/Cas9 Addresses Disease at the Genetic Level AAAA Lipid Nanoparticles (LNPs) Key Advantages of LNP Delivery • Large cargo capacity for CRISPR/Cas9 AAAA Albumin • Transient expression gRNA Cas9 mRNA • Scalable synthetic manufacturing Target-specific gRNA

  4. Slide 4: Precise Gene Insertion Has the Potential to Overcome Limitations of Traditional Gene Therapy

    Precise Gene Insertion Has the Potential to Overcome Limitations of Traditional Gene Therapy AAV generally does not Adeno-associated Antibodies integrate into the genome; Lenti/retro virus virus (AAV) expression is transient in dividing cells AAV exposure generates antibodies; prevents potential re-

  5. Slide 5: CRISPR Delivery with LNPs and AAV as Template is an Effective Modular Approach

    CRISPR Delivery with LNPs and AAVAAAA as Template is an Effective Modular Approach for Targeted, Stable DNA Insertion for Range of Genetic Diseases Lipid nanoparticles Adeno-associated virus Albumin (LNPs) gRNA (AAV) AAAA F9 DNA Template Cas9 Cas9 mRNA A A A A A A A A A A Hybrid LNP-AAV delivery sys

  6. Slide 6: F9 is Ideal Model System for Evaluating Targeted Insertion

    F9 is Ideal Model System for Evaluating Targeted Insertion • Hemophilia B is well-characterized • Clearly defined benchmarks • Real-time biomarker measurement • Replacement therapy established 6

  7. Slide 7: Human Factor 9 (F9) Model System Used to Investigate In Vivo Insertion at Albumin Intron Safe Harbor Site

    Human Factor 9 (F9) Model System Used to Investigate In Vivo Insertion at Albumin Intron Safe Harbor Site AAV Bi-directional, LNP (Cas9/gRNA) insertion template Promoter Exon 1 Exon 2 SA SA Human F9 pA pA Human F9 Alb Promoter PP SP SA SA Human F9 Exon 1 pA pA Human F9 Exon 2 Alb mRNA Human F9 AAAAA

  8. Slide 8: Circulating Human FIX Protein Levels in Mice Are Dependent on Guide Used for Insertion

    Circulating Human FIX Protein Levels in Mice Are Dependent on Guide Used for Insertion Mild 8 Hemophilia B3

  9. Slide 9: Circulating Human FIX Protein Levels in Adult Mice Can be Regulated by Titrating the Dose of LNP and AAV

    Circulating Human FIX Protein Levels in Adult Mice Can be Regulated by Titrating the Dose of LNP and AAV Elements that determine LNP circulating human FIX protein levels: 1. Guide RNA sequence to vary genomic insertion site 2. AAV dose that delivers inserted gene DNA sequence 3. LNP dose that delive

  10. Slide 10: Targeted Insertion Results in High Frequency (~50%) of Liver Cells that Contain F9 mRNA in Adult Mice

    Targeted Insertion Results in High Frequency (~50%) of Liver Cells that Contain F9 mRNA in Adult Mice Albumin ZZ Exon 1 Exon 2 Transcription Splicing Albumin ZZ Exon 1 Exon 2 (ZZ: BaseScope™ paired oligo probes) mAbl-F9 mRNA positive cells* ~50% 10 * Quantification with HALO image process

  11. Slide 11: FIX Levels in Adult Mice Are Stable Out to Months in Ongoing 1-Year Durability Study

    FIX Levels in Adult Mice Are Stable Out to 10 Months in Ongoing 1-Year Durability Study 11

  12. Slide 12: Physiologically Normal Levels of Circulating Human FIX Protein Achieved With Insertion of F9 in NHPs and Maintained Through Day 28

    Physiologically Normal Levels of Circulating Human FIX Protein Achieved With Insertion of F9 in NHPs and Maintained Through Day 28 Normal range of circulating human FIX protein levels2 Baseline albumin levels maintained at ND ND ND day 28 Buffer AAV alone LNP alone gRNA101 gRNA101 + AAV1 + AAV1 Impr

  13. Slide 13: Key Takeaways

    • CRISPR delivery with LNPs and AAV as a DNA donor transgene template achieves normal circulating human FIX protein levels in NHPs Key Takeaways • Varying LNP or AAV doses, with choice of insertion site, allows for regulation of FIX levels in adult mice • Sustained 10-month human FIX durability in a

  14. Slide 14: Acknowledgements

    Acknowledgements Intellia team Seth Alexander Brad Murray Jonathan Nolasco Jessica Seitzer Adam Amaral Anne Harris Daniel O’Connell Cindy Shaw Peter Bialek Denisse Hernandez Merouane Ounadjela Samantha Soukamneuth Carri Boiselle Jane Van Heteren Spurthi Patil Srijani Sridhar Vinita Doshi Hon-Ren Hua

  15. Slide 15: Intellia Therapeutics

    Intezia THERAPEUTICS

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