Editas Medicine, Inc. · NASDAQ:EDIT

Editas Medicine — European Hematology Association 2020

13 slides from Editas Medicine's conference presentation, June 2020

  1. Slide 1: EDIT-301: An Autologous Cell Therapy to Promote Fetal Hemoglobin Expression for Sickle Cell Disease

    EDIT-301: AN AUTOLOGOUS CELL THERAPY TO PROMOTE FETAL HEMOGLOBIN EXPRESSION FOR THE POTENTIAL TREATMENT OF SICKLE CELL DISEASE Jack Heath, Edouard de Dreuzy, Patricia Sousa, John A Zuris, Ramya Viswanathan, Sean Scott, Jen Da Silva, Terence Ta, Tongyao Wang, Harry An, Tamara Monesmith, Christopher J

  2. Slide 2: Disclosures

    Disclosures Jack Heath is a full-time employee and shareholder in Editas Medicine © 2020 Editas Medicine 2

  3. Slide 3: Overview

    Overview Desirable Editing with Highly Efficient, Inducing Anti-Sickling Cas12a at the HBG1/2 Productive and Durable Fetal Hemoglobin to Promoter in a Region Editing and an Improved Treat Sickle Cell Where Fetal Hemoglobin Phenotype in Edited Disease Inducing Mutations Sickle Patient Red Blood Natur

  4. Slide 4: Harnessing Natural Anti-Sickling Hemoglobin to Treat Sickle Cell Disease

    Harnessing Natural Anti-Sickling Hemoglobin to Treat Sickle Cell Disease Embryo Fetus Adult HBE HBG2 HBG1 HBD HBB b-globin locus Insulator Enhancer Insulator (5’HS) (HS1-4) (3’HS1) LCR a a a a g g b s s b HbF HbS % Globin Synthesis Globin Onset of SCD switch Symptoms Months Post-conception Adapted f

  5. Slide 5: Naturally Occurring Mutations Support Clinical Relevance and Safety of Editing at the HBG1/2 Promoter Region

    Naturally Occurring Mutations Support Clinical Relevance and Safety of Editing at the HBG1/2 Promoter Region Embryo Fetus Adult HBE HBG2 HBG1 HBD HBB b-globin locus Insulator Enhancer Insulator (5’HS) (HS1-4) (3’HS1) LCR Multiple Naturally Occurring HbF Inducing Mutations located in HBG Distal CCAAT

  6. Slide 6: Large NHEJ Deletions at HBG Distal CCAAT Box Region Are Durable and Induce High Levels of HbF

    Large NHEJ Deletions at HBG Distal CCAAT Box Region Are Durable and Induce High Levels of HbF Long-Term HSCs Rely Heavily on Larger Deletions are More Productive NHEJ-mediated Editing >3 bp deletions – elevated HbF HbF (Gg/ b-like %)* > 3bp NHEJ deletions induce long-term, robust HbF expression * On

  7. Slide 7: Cas12a Demonstrates a Superior Editing Profile to SpCas9 at HBG Distal CCAAT Box Region

    Cas12a Demonstrates a Superior Editing Profile to SpCas9 at HBG Distal CCAAT Box Region for Persistent and High HbF Expression Enzyme Cleavage Sites NHEJ Indels © 2020 Editas Medicine 7

  8. Slide 8: Cas12a Editing is Efficient and Results in Long-Term Robust and Pancellular HbF Expression In Vivo

    Cas12a Editing is Efficient and Results in Long-Term Robust and Pancellular HbF Expression In Vivo n=5 HbF (g/b-like %) Editing n=5 In vivo n=1 HbF Expression n=5 n=5 F + RBC (%) In vivo HbF-positive RBCs (F-cells) n=5 Data from one representative experiment © 2020 Editas Medicine 8

  9. Slide 9: Cas12a Edited CD34+ Hematopoietic Stem Cells Provide Stable, Polyclonal Engraftment with No Lineage Skewing

    Cas12a Edited CD34+ Hematopoietic Stem Cells Provide Stable, Polyclonal Engraftment with No Lineage Skewing Engraftment Blood Bone Marrow Mock Edited 20 Weeks 16 weeks post infusion. n = 5 mice / group Representative data from one mouse © 2020 Editas Medicine 9

  10. Slide 10: Comparable Editing and Robust HbF Induction Achieved in Normal and Sickle Donor CD34+ Cells

    Comparable Editing and Robust HbF Induction Achieved in Normal and Sickle Donor CD34+ Cells (EDIT-301) Editing Ex vivo HbF Expression HbF (g/b-like %) Indels (%) Untreat Edited Untreat EDIT-301 Untreat Edited Untreat EDIT-301 Normal Donor Sickle Donor Normal Donor Sickle Donor n=3 n=4 n=3 n=4 Effici

  11. Slide 11: EDIT-301 RBCs from Sickle Patient Donors Have Significantly Reduced Sickling

    EDIT-301 RBCs from Sickle Patient Donors Have Significantly Reduced Sickling, Lower Point of Sickling and Improved Deformability Improved Deformability Reduced Sickling Lowered Point of Sickling at Low O2 Untreat EDIT-301 Untreat EDIT-301 Untreat EDIT-301 HbF 19.9% HbF 53.8% HbF 19.9% HbF 53.8% HbF

  12. Slide 12: Conclusions

    Conclusions Cas12a demonstrates a superior editing profile to SpCas9 at HBG distal CCAAT box region for persistent and high HbF expression Potentially therapeutically-relevant levels of HbF were expressed long-term with pancellular distribution in vivo High levels of editing were achieved with EDIT-

  13. Slide 13: Acknowledgements

    Acknowledgements Editas Medicine Mingli Li, Francis Awokang, Pratik Randeria, Daniel Nguyen, Gwen Wilmes, Emmett Hedblom, Daniel Leblanc, Ash Mondkar, Jacqueline Nelson, Krithika Murali, Gwynneth Borges, Mingli Li, Arun Bhattathiri, Deep Majithia, Faith Barnard, Raisa Lowe, Shahzad Master, Benjamin

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