Beam Therapeutics Inc. · NASDAQ:BEAM

Beam Therapeutics — Technical Presentation (December 2020)

12 slides from Beam Therapeutics's technical presentation, December 2020

  1. Slide 1: Adenine Base Editing of Gamma Globin Gene Promoters Shows no Detectable Off-Target RNA or DNA Editing

    Adenine Base Editing of Gamma Globin Gene Promoters Shows no Detectable Off-Target RNA or DNA Editing L i n g L i n * , L a u r e n Yo u n g * , J e n n y O l i n s * , J e r e m y D e c k e r, A l e x a n d e r J . L i q u o r i , S . Yi n g y i n g Z h a n g , H a i h u a C h u , D a i s y L a m ,

  2. Slide 2: Disclosure

    Disclosure • I and all authors are Beam employees and shareholders

  3. Slide 3: Sickle Cell Disease (SCD)

    Sickle Cell Disease (SCD) β-globin gene T-to-A mutation causes sickling Adult β-globin HBB Sickle β-globin HBB gene gene Glutamic acid at Valine at 6th amino acid CTC 6th amino acid C AC (HbA) G AG (HbS) GTG Pain crises Normal red Sickling red Organ damage blood cells blood cells Hemolysis Anemia Ap

  4. Slide 4: BEAM-101: Recreating Hereditary Persistence Of Fetal Hemoglobin (HPFH) With Base Editing

    BEAM-101: Recreating Hereditary Persistence Of Fetal Hemoglobin (HPFH) With Base Editing Sickle cell disease patient Reactivating fetal hemoglobin genes X HBG2 X HBG1 HBB HBG2 HBG1 HBB Fetal Fetal Adult γ-globin γ-globin sickle β- (HbF) (HbF) globin (HbS) A→G X X ABE edits regulatory element Repress

  5. Slide 5: Adenine Base Editing Technology

    Adenine Base Editing Technology CRISPR • Adenine Base Editor (ABE) comprises a deaminase enzyme fused to catalytically impaired CRISPR protein. T • Guide RNA (gRNA) directs the ABE to a target genomic DNA sequence and A Deaminase exposes the editing window. A • Deaminase chemically converts target a

  6. Slide 6: Strategy of Off-Target Editing Assessment

    Strategy of Off-Target Editing Assessment Guide-dependent Guide-independent Guide-independent Guide-dependent In-silico Analysis Spurious RNA deamination • 42,804 potential sites • mRNAseq identified • 96h post electroporation ONE-Seq Spurious DNA deamination • 3,773 sites prioritized from in- • CFU

  7. Slide 7: Guide-Dependent Off-target Assessment Shows No Significant Off-targets

    Guide-Dependent Off-target Assessment Shows No Significant Off-targets A B 8000 MEAN_CPM 6000 4000 Rep 1 2000 0 10000 8000 Rep 2 MEAN_CPM 6000 4000 2000 0 Sequence • 143 sites selected for testing in cells using rhAmpSeq • 90% of potential sites have >10k reads sequencing coverage • Only on-target e

  8. Slide 8: Guide-Independent RNA Editing Shows No Difference Between Edited And Unedited Groups

    Guide-Independent RNA Editing Shows No Difference Between Edited And Unedited Groups A A>G editing (%) 80 B 1.0 DNA on-target 60 A>I editing (%) 0.8 40 0.6 RNA 0.4 20 0.2 0 0.0 .2 s g A sg N A A N 5u sg ed /0 M RN N m A/ uM eat uM R R Rep.1 Rep.2 Rep.1 Rep.2 Rep.1 Rep.2 Rep.1 Rep.2 N 5 r ABE nM R /

  9. Slide 9: Guide-Independent DNA Editing Shows No Significant Enrichment Of A > G Mutations

    Guide-Independent DNA Editing Shows No Significant Enrichment Of A > G Mutations A B Electroporation C Whole genome sequencing 80 -48 h 0h 48 h 96h with 30x genome coverage A>G editing (%) Relative Mutation Rate DNA on-target Whole 60 CFU assay genome D14 sequencing (odds-ratio) (WGS) 40 20 0 d h h

  10. Slide 10: Guide-Independent DNA Editing Shows No Significant Enrichment of A > G Mutations In CD34+ HSPCs

    Guide-Independent DNA Editing Shows No Significant Enrichment of A > G Mutations In CD34+ HSPCs Reference Base ABE ABE ABE ABE Alternate Base • WGS studies show mutational classification of all somatic mutations observed genome wide in single clones. • No significant difference between edited and un

  11. Slide 11: Key Takeaways

    Key Takeaways ✓ No guide-dependent DNA off-target editing • Comprehensive determination of all the potential off-target editing using ONE-seq • Further validation of actual editing in CD34+ HSPCs edited at supra-saturating dose revealed no off-target DNA editing in ABE edited cells ✓ No guide-indepe

  12. Slide 12: Thank you !

    Thank you ! V I S I T B E A M T X . C O M F O R M O R E I N F O R M AT I O N .

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