Omniab, Inc. · NASDAQ:OABI

Omniab — Technical Presentation (December 2021)

28 slides from Omniab's technical presentation, Dec 13, 2021

  1. Slide 1: re o f= = o o <= c oO ie AS aad

    re o f= = o o <= 7 c oO ie AS aad

  2. Slide 2: Discovery, Expression, and Characterization of Neutralizing Picobodies against SARS-CoV2

    Discovery, Expression, and Characterization of Neutralizing Picobodies against SARS-CoV2 Antibody Engineering and Therapeutics Dec. 13, 2021 Vaughn Smider, M.D., Ph.D. President Applied Biomedical Science Institute

  3. Slide 3: Cows have long CDR H3s, with an ultralong subset (40-70 amino acids)

    Cows have long CDR H3s, with an ultralong subset (40-70 amino acids) murine Proportion human bovine 10 20 30 40 50 60 70 CDR H3 length 3

  4. Slide 4: Cow ultralong CDR H3s have protruding 'stalk' and 'knob' minidomains

    Cow ultralong CDR H3s have protruding ‘stalk’ and ‘knob’ minidomains PDB: 3giz PDB:4k3d Stanfield, et al. (2017) Adv Immunol, 137: 135 Wang et.al. (2013) Cell 153: 1379-1393 4

  5. Slide 5: Structures reveal conserved and diverse features of ultralong CDR H3s

    Structures reveal conserved and diverse features of ultralong CDR H3s E03 B11 BLV1H12 BLV5B8 A01 Length: 44 63 61 56 61 Cys: 2 8 6 6 6 Pattern: 1-2 1-4, 2-7, 3-8, 5- 1-4, 2-6, 3-5 1-3, 2-4, 5-6 1-4, 2-5, 3-6 6 Stanfield, et.al. (2016) Science Immunology: 1(1) 5

  6. Slide 6: Ultralong CDR H3 sequences are enormously diverse

    Ultralong CDR H3 sequences are enormously diverse Wang et.al. (2013) Cell 153: 1379-1393 6

  7. Slide 7: Cows are the only species that can rapidly produce broadly neutralizing antibodies against HIV

    Cows are the only species that can rapidly produce broadly neutralizing antibodies against HIV Sok et.al. (2017) Nature 548: 108-111 7

  8. Slide 8: NC-Cow1 Ultralong CDR H3 binds the recessed CD4 epitope on HIV Env

    NC-Cow1 Ultralong CDR H3 binds the recessed CD4 epitope on HIV Env Stanfield, et.al. (2020) Sci Adv 6(20): eaba0468. 8

  9. Slide 9: Target binding domains of biologics and small molecules

    Target binding domains of biologics and small molecules antibodies vNAR Most species Fv VHH Knob Cyclotide Cyclosporine Imatinib 25 kDa 15 kDa 4.4 kDa 3.5 kDa 1.2 kDa 0.49 kDa Small molecule Cyclic peptide Sharks Camelids -Plant protease inhibitors -Venom peptides (ion channel inhibitors) Cows -“Kno

  10. Slide 10: Can we produce knobs independently of the antibody?

    Can we produce knobs independently of the antibody? MacPherson A., et.al. eLife (2021) 10:e63586 From one immunization, we can potentially discover two classes of therapeutic: IgG, peptide “knob” 10

  11. Slide 11: Features of cow antibody-derived peptide (picobody) knobs

    Features of cow antibody-derived peptide (picobody) knobs Ultralong CDR3 cow antibody “knob” peptide CDR3  Small - tiny size approaches small molecules Better tissue penetration, alveolar delivery  Target binding - high affinity and epitope coverage, like antibodies  Stable and Developable Rigi

  12. Slide 12: Discovery of cow anti-coronavirus antibodies

    Discovery of cow anti-coronavirus antibodies Spike mAbs knobs Spike immunized cow 12

  13. Slide 13: A novel phage display system to discover antibodies and knobs

    A novel phage display system to discover antibodies and knobs Fixed light chain scFv “knob” IgG (chimeric or humanized) Peptide “knob” Phage ELISA IgG ELISA (titration) Pseudovirus neutralization Live virus PRNT 13

  14. Slide 14: Ultralong CDR H3s bind SARS-CoV-2 variants

    Ultralong CDR H3s bind SARS-CoV-2 variants Selected on Beta (later) 14

  15. Slide 15: Most antibodies cross-react with SARS-CoV-2 variant strains

    Most antibodies cross-react with SARS-CoV-2 variant strains SKD and SKM completely lose binding against beta 15

  16. Slide 16: Ultralong CDR H3 antibodies maintain neutralization activity against SARS-CoV-2 variant strains

    Ultralong CDR H3 antibodies maintain neutralization activity against SARS-CoV-2 variant strains Wild-type Beta Delta 120 120 120 2G3 2G3 2G3 2G3 100 F12 100 F12 100 F12 F12 SKD SKD SKD SKD 80 SKM 80 SKM 80 SKM SKM RLU (% mock) RLU (% mock) RLU (% mock) R4C1 R4C1 4C1 R4C1 60 R5C1 60 R5C1 60 5C1 R5C1

  17. Slide 17: 2D9 (selected on beta) is equally active against wt, beta, and delta variants

    2D9 (selected on beta) is equally active against wt, beta, and delta variants 120 100 RLU (% mock) 80 WT Beta 60 Delta 40 20 0 -2 -1 0 1 2 Log10 (ng/ml) of Ab 17

  18. Slide 18: Preliminary structural biology – EM

    Preliminary structural biology – EM Andrew Ward lab, Scripps Research 18

  19. Slide 19: 2G3 prevents SARS-CoV-2 infection in vivo

    2G3 prevents SARS-CoV-2 infection in vivo single IP dose before infection, K18 ACE2 Tg model John Teijaro lab, Scripps Research 19

  20. Slide 20: Can we produce knobs independently of the antibody?

    Can we produce knobs independently of the antibody? MacPherson A., et.al. eLife (2021) 10:e63586 20

  21. Slide 21: A straightforward, scalable, knob production process in E.coli

    A straightforward, scalable, knob production process in E.coli 21

  22. Slide 22: Purified knobs- some knobs are stable to heat and SDS

    Purified knobs- some knobs are stable to heat and SDS aprotinin SKM 2G3 4C1 2D9 F12 2D9 80 50 40 9 SDS-PAGE Coomassie (+DTT) Modified western detected with biotinylated RBD (-DTT) 22

  23. Slide 23: Independently expressed 'knobs' neutralize SARS-CoV-2

    Independently expressed “knobs” neutralize SARS-CoV-2 Knob molecular evolution 23

  24. Slide 24: Next steps

    Next steps  Define start and end of knobs (Gabrielle Warner poster)  Stability studies (serum, proteases, pH, etc.), oral availability?  Intranasal/inhaled animal model(s)  PK, PD, Production process, scale (Dianne Retallack – next!)  More knobs against emerging strains, cross coronavirus neutr

  25. Slide 25: Picobodies as building blocks for novel therapeutics

    Picobodies as building blocks for novel therapeutics 25

  26. Slide 26: Conclusions

    Conclusions  We have discovered extremely potent (pM) antibodies targeting coronavirus SARS-CoV-2 - 2G3, F12, 2D9 (very potent) cross-react with SA strains - 4C1, 5C1 (less potent, still ~nM) cross-react with SARS-CoV-1  Most potent mAbs have “ultralong” CDR H3 regions (>60 amino acids)  “Knob” r

  27. Slide 27: Acknowledgements

    Acknowledgements Smider Lab / ABS Institute Scripps Dennis Burton Devin Sok Kansas State University Fangzhu Zhao Waithaka Mwangi Riqui Huang K.C. Cheong Ian Wilson Yunjeong Kim Gabrielle Warner Robyn Stanfield Duncan McGregor Andrew Ward Abigail Kelley Jonathan Torres Alexandra Stambaugh Abigail Jac

  28. Slide 28: Thank You!

    Thank You! Vaughn Smider M.D., Ph.D. https://www.omniab.com/ vaughn.smider@absinstitute.org https://absinstitute.org/ 28

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