Omniab, Inc. · NASDAQ:OABI
Omniab — Technical Presentation (October 2020)
32 slides from Omniab's technical presentation, Oct 29, 2020
Slide 1: OmniAb Technology Suite
1 OmniAb Technology Suite Expanding our best-in-class status with innovation and new technology offerings Naturally optimized human antibodies The only four species Bispecific platforms platform High demand for bispecific antibodies Industry-first ultralong CDR-H3s Recent technology additions Indust
Slide 2: OmniTaur: Ultralong CDR3 Cow Antibodies for Challenging Targets
OmniTaur : Ultralong ™ CDR3 Cow Antibodies for Challenging Targets Vaughn V. Smider M.D., Ph.D. October 29, 2020
Slide 3: Novel antibody paratopes have evolved in different species
3 Novel antibody paratopes have evolved in different species Organism Binding Structure Echinodermata sea urchin binding surface Innate Immunity Variable Lymphocyte Receptors Agnatha lamprey H3 H1 Single Chain IgNAR Vertebrata Chondrichthyes shark L1 Immunoglobulins Ig Gene Conversion in Bursa of Fa
Slide 4: Unique cow antibody structures enable binding to challenging targets
Unique cow antibody structures enable binding to challenging 4 targets CDR3 ▼ Novel cow antibody structure ‒ Could enable targeting crevices, pores, channels, or other epitopes that “regular” antibodies cannot; two approaches: 1. Cow immunization to select novel structures 2. Knob engineering with b
Slide 5: Expanding target and epitope space: a fraction of potential targets are addressed
Expanding target and epitope space: a fraction of potential 5 targets are addressed by current modalities Current Antibody Discovery GPCRs Ion Channels TNF IgE VEGF Soluble Proteins Pores/Pumps Extracellular Domains Her2 EGFR CTLA4 Cow antibody scaffold uniquely suited for Multiprotein Complexes cry
Slide 6: Why cow antibodies?
6 Why cow antibodies? murine human Proportion bovine 10 20 30 40 50 60 70 CDR H3 length ▼ The widest range of CDR3 length of any species ‒ the longest CDR3s known (10% of the repertoire between 40-70 residues - ‘ultralong’) ‒ enhanced structural diversity ‒ protruding structures for binding challeng
Slide 7: Cow antibodies have the longest CDR H3s
7 Cow antibodies have the longest CDR H3s
Slide 8: Five structures reveal conserved and diverse features of ultralong CDR H3s
Five structures reveal conserved and diverse features of 8 ultralong CDR H3s Length: 44 63 61 56 61 Cys: 2 8 6 6 6 Pattern: 1-2 1-4, 2-7, 3-8, 5-6 1-4, 2-6, 3-5 1-3, 2-4, 5-6 1-4, 2-5, 3-6 Stanfield, et.al. (2016) Science Immunology: 1(1)
Slide 9: A conserved 3-strand core forms a scaffold for two highly diverse loops
A conserved 3-strand core forms a scaffold for two highly 9 diverse loops and disulfide “CDR-like” loops? Diversity in: • Sequence content • Length • Shape/disulfide connectivity
Slide 10: Ultralong CDR H3 sequences are enormously diverse
10 Ultralong CDR H3 sequences are enormously diverse Wang et.al. (2013) Cell 153: 1379-1393
Slide 11: Loops within ultralong CDR H3s may be CDRs themselves
11 Loops within ultralong CDR H3s may be CDRs themselves CDR = Complementarity Determining Region CDR Loops? CDR Loops
Slide 12: Cow antibodies have unique structural diversity
12 Cow antibodies have unique structural diversity Stanfield, et al. (2017) Adv Immunol, 137: 135 Wang et.al. (2013) Cell 153: 1379-1393
Slide 13: OmniTaur discovery platforms
13 OmniTaur discovery platforms ▼ Immunization ‒ Single-cell VH and VL cloning, expression ‒ Phage display antigen Monoclonal antibody discovery ▼ Customized “knob” engineering (libraries, bioactive peptides, etc.)
Slide 14: Cow antibodies with ultralong CDR3s can target the challenging antigen, HIV gp120
Cow antibodies with ultralong CDR3s can target the challenging 14 antigen, HIV gp120 Sok et.al. (2017) Nature 548: 108-111
Slide 15: Can cows develop broadly neutralizing antibodies against HIV?
15 Can cows develop broadly neutralizing antibodies against HIV? Neutralizing Antibodies? HIV gp120 (BG505 Env)
Slide 16: Serum Neutralization Breadth Against Multiple HIV-1 strains
16 Serum Neutralization Breadth Against Multiple HIV-1 strains Sok, D. et al. Nature (2017) 548: 108
Slide 17: Ultralong CDR H3s were selected
17 Ultralong CDR H3s were selected 100 90 80 70 60 50 Percent 40 30 20 10 0 Short Ultralong Short Ultralong Non-Immunized Cows BG505 Immunized Cows, BG505 sorted
Slide 18: Monoclonal antibodies utilize ultralong CDR H3s
18 Monoclonal antibodies utilize ultralong CDR H3s Sok, D. et al. Nature (2017) 548: 108
Slide 19: NC-Cow1 binds the CD4 binding site
19 NC-Cow1 binds the CD4 binding site Sok, D. et al. Nature (2017) 548: 108
Slide 20: NC-Cow1 Ultralong CDR H3 Binds the Recessed CD4 Epitope on HIV Env
NC-Cow1 Ultralong CDR H3 Binds the Recessed CD4 Epitope 20 on HIV Env Stanfield, et.al. Sci Adv (2020) 6(20): eaba0468.
Slide 21: Cow antibodies with ultralong CDR H3s have very high affinity
21 Cow antibodies with ultralong CDR H3s have very high affinity IgG KD (M) ka (1/Ms) kd (1/s) NC-Cow-1 4.198x10-12 5.592x105 2.347x10-6 P1F1 4.640x10-11 6.508x106 3.020x10-4 P3H4 1.237x10-10 1.315x106 1.626x10-4 P4F8 9.987x10-12 2.459x106 2.456x10-5 P4G8 1.345x10-11 1.829x106 2.460x10-5
Slide 22: Cow anti-coronavirus SARS-CoV-2 antibodies
22 Cow anti-coronavirus SARS-CoV-2 antibodies Receptor Binding Domain (RBD) Serum Cow #1: RBD immunized PBMCs mAbs Cow #2: Spike immunized Spike Two human “common cold” coronaviruses evolved after species transfer from cow (BCoV) to humans
Slide 23: Cow anti-SARS-CoV-2 antibody discovery
23 Cow anti-SARS-CoV-2 antibody discovery Long Ultralong Proportion 10 20 30 40 50 60 70 CDR H3 length Binding Pseudovirus Neutralization
Slide 24: Natural peptides that inhibit ion channels are similar to cow antibody knob domains
Natural peptides that inhibit ion channels are similar to cow 24 antibody “knob” domains Shk peptide RSCIDTIPKSRCTAFQCKHSMKYRLSFCRKTCGTC Cow antibody “knob” SCPDGYRERSDCSNRPACGTSDCCRVSVFGNCLTT
Slide 25: An engineered cow antibody specifically inhibits the ion channel Kv1.3
An engineered cow antibody specifically inhibits 25 the ion channel Kv1.3 100 Kv1.3 80 % Inhibition 60 40 Kv1.5 20 Kv1.5 vehicle 0 Kv1.3 vehicle -20 -10 -9 -8 -7 -6 -5 Log [M] Electrophysiology, IC50 ~ 140-310 pM
Slide 26: Cow antibody humanized scaffold
26 Cow antibody humanized scaffold ▼ 95% identical to human germline outside CDR H3 (heavy chain) ▼ 90% identical to human germline (light chain) Red = stabilizing cow residues Blue = human
Slide 27: OmniTaur Intellectual Property
27 OmniTaur Intellectual Property ▼ 22 granted or issued patents internationally ▼ Broad coverage of ultralong CDR H3 antibody compositions and sequences ▼ Key compositions and motifs enabling humanized scaffolds ▼ Internal Patents acquired from Taurus Biosciences and the Scripps Research Institute
Slide 28: Summary
28 Summary ▼ OmniTaur is a cutting-edge antibody platform based on the novel long CDR H3 structure of humanized cow antibodies ‒ Challenging targets/epitopes ▼ Discovery can occur through immunization and ‒ Single-cell PCR of VH and VL, expression, and screening ‒ Phage Display ▼ The knob domain is
Slide 29: OmniAb Platform
29 29 OmniAb® Platform Single license provides access to full suite of discovery technologies OmniAb partners enjoy • Ab Initio Antigen – proprietary methods for purifying multi-Tm and other difficult proteins for immunization and screening evergreen access to the • OmniRat®, OmniMouse®, and OmniChi
Slide 30: Acknowledgements
30 Acknowledgements Smider Lab / ABS Institute Current Riqui Huang Jeremy Haakenson Gabrielle Warner Duncan McGregor Abigail Kelley Biura Markanian Gorune Gorolian Recent Melissa Vadnais Jason Higa Erik Wold Wenyong Tong Veronica Verplancken Funding: NIH, DoD, American Cancer Society, USDA
Slide 31: Collaborators
31 Collaborators Scripps Andrew Ward Jonathan Torres Dennis Burton Ali Torkamani Devin Sok Peter Schultz Feng Wang Khoa Le Karen Saye-Francisco Texas A&M Joseph Jardine Michael Criscitiello Jennifer Ruiz Thad Deiss Alejandro Ramos Patricia Chen Chi-Hui Lang Kansas State University Waithaka Mwangi Ia
Slide 32: Thank you!
Thank you! Offni leur