Omniab, Inc. · NASDAQ:OABI
Omniab — 10th Annual World Bispecific Summit 2019
19 slides from Omniab's conference presentation, Sep 17, 2019
Slide 1: OmniFlic and OmniClic: Transgenic Rat and Chicken Platforms for Human Bispecific Antibody Discovery
OmniFlic and OmniClic: Transgenic Rat and Chicken Platforms for Human Bispecific Antibody Discovery Christel Iffland Kathryn Ching 10th Annual Summit World Bispecific September 17-19, 2019 |Boston, MA
Slide 2: Five Platforms Three Species One License
2 Five Platforms Three Species ™ One License
Slide 3: OmniAb
3 OmniAb® Best-In-Class Antibody Discovery Technology Epitope coverage • Human Ig-transgenic animals leveraged across 3 species ‒ OmniRat®, OmniMouse®, OmniChicken® ‒ OmniFlic® (rat) and OmniClic™ (chicken) for bispecific applications Mouse Rat • Each platform with optimized human V genes ‒ 100% VH
Slide 4: Rodent Platform Development
4 Rodent Platform Development Knock-out of rat Ig genes ̶ Heavy chain J-locus ̶ Light chain Ck ̶ Light chain Cl Human LC locus Heavy chain locus Rat constant VL…………..VL1 J CL + VH…..VH1 D J EµCµCg1 Cg2b e a Knock-out of mouse Ig genes ̶ Heavy chain J-locus ̶ Light chain Ck VJ C VDJ C mRNA Human Anti
Slide 5: OmniFlic for Easier Bispecific Antibody Production
5 OmniFlic for Easier Bispecific Antibody Production Common Light Chain Solves the Light Chain Pairing Challenge HC14 Monospecific IgG HC (44 VH) HC30 KJ 15 Ig V3- Ig 1-5 E KC KD K Ig A UR Rearranged human k L-chain expressed with any (human) IgH locus Bispecific IgG
Slide 6: Rodent Platforms
6 Rodent Platforms • 100% VH and >70% VL human germline diversity • High diversity of sequences by ‒ Mixed genetic background (Lewis/Brown Norway/Sprague Dawley and B6/SJL) ‒ Productive VDJ and VJ recombination • High affinities and good manufacturability by somatic mutations • Functional activity a
Slide 7: Current and Upcoming Transgenic Chicken Platforms
7 Current and Upcoming Transgenic Chicken Platforms Light Chain “C” VK3-15 “HCO” Heavy Chain “C” V3-23 V3-23 Light Chain “E” OmniClic™ VL1-44 VK3-15 Light Chain “C” VK3-15 “Novel scaffold” Heavy Chain “SD” TBD V3-23 Light Chain “E” VL1-44 In development: Heavy Chain Only scaffold Common LC antibodie
Slide 8: OmniClic™: Tg Chickens with Common Light Chain
8 OmniClic™: Tg Chickens with Common Light Chain Engineered for Bispecific Antibody Discovery and Development CmLC1 SynVH • Common light chain based upon human VK3-15 scaffold ‒ Active V gene fully germline ‒ Pseudogenes also germline with no CDR sequence diversity ‒ Either 1 or 4 active gene copies
Slide 9: OmniClic Birds Have Normal B Cell Populations in the Periphery
9 OmniClic Birds Have Normal B Cell Populations in the Periphery PBL at 6 Weeks CmLC1 CmLC4 % cells stained % cells stained
Slide 10: CmLC-Expressing Birds Demonstrate Robust Titers Against Human Progranulin
10 CmLC-Expressing Birds Demonstrate Robust Titers Against Human Progranulin 45211 CmLC1/SynVH-C 45359 CmLC1/SynVH-SD 4 4 Preimmune Preimmune Draw 1 Draw 1 Draw 2 Draw 2 3 Draw 3 3 Draw 3 Final Draw Final Draw OD450 OD450 2 2 1 1 0 0 102 103 104 105 106 107 102 103 104 105 106 107 Fold dilution Fold
Slide 11: Broad Epitope Coverage: High-Throughput SPR (Carterra)
11 Broad Epitope Coverage: High-Throughput SPR (Carterra) OmniClic Regular OmniChicken (VK3-15/VH3-23 SD): anti-His G p F Anti-His ? CD p CD E G F E B A G? ? A 45 mAbs + 32 Stds B All bins (except p) were populated in CmLC cohort 74 CmLC1 mAbs + 28 Stds
Slide 12: Epitope Bins Are Correlated With Sequence Groups
Epitope Bins Are Correlated With 12 12 Sequence Groups Bin Ms-X B B B B No No No No B No B No A Yes A Yes A Yes A Yes A Yes = has germline VK B Yes B Yes B Yes B Yes B Yes B Yes CD No CD No CD No CD No CD No • All subdomains are recognized by CD No A No A No E No E No mAbs with germline VK E No E No
Slide 13: Diversity Is Focused on the Heavy Chain
13 Diversity Is Focused on the Heavy Chain 100 Chart Title 90 VK 80 70 60 50 Chart Title 100 40 . 30 90 W 20 Y 80 F 10 M 70 0 E I V M T Q S P A T L S V S P G E R A T L S C R A S Q S V S S N L A W Y Q Q K P G Q A P R L L I Y G A S T R A T G I P A R F S G S G S G T E F T L T I S S L Q S E D F A V Y Y
Slide 14: Antigen-Specific Clones Show Little Amino Acid Diversity on the Light Chain
14 Antigen-Specific Clones Show Little Amino Acid Diversity on the Light Chain SynVK-CK CmLC1 SynVK-CK-SynVH-C Mean, S.D. CmLC1/SynVH-C Mean, S.D. VK 9.6+-3.4 40 VK 2.7+-3.3 40 VH 12.5+-2.6 VH 14.5+-3.9 Percent of clones Percent of clones 30 30 20 20 10 10 0 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 1
Slide 15: Isoaffinity Plot Colored by Epitope Bin
15 Isoaffinity Plot Colored by Epitope Bin 10 pM 100 pM 1 nM 10 nM 100 nM ka (1/Ms) 1 µM kd (1/s) Isoaffinity plot, 71 mAbs (46 analyzed in duplicate)
Slide 16: Subnanomolar Affinities From OmniClic-Derived Antibodies
16 Subnanomolar Affinities From OmniClic-Derived Antibodies OmniClic OmniChicken 10000 10000 1000 1000 KD (nM) KD (nM) 100 100 10 11.8 10 6.2 4.2 1 1 0.1 0.1 VK VK 23 3- e e H tiv lin /V na rm 15 ge 3- VK
Slide 17: CmLC-Derived Antibodies Reformatted with Germline VK Retain Epitope Specificity and Affinity
17 17 CmLC-Derived Antibodies Reformatted with Germline VK Retain Epitope Specificity and Affinity • A subset of clones were re-expressed 103 with the germline VK KD (nM) with germline VK m=1 • Epitope bin assignments were not 102 affected 101 • No clones were lost • For most clones, affinities were
Slide 18: Conclusions
18 Conclusions • OmniChickens retain the antigen recognition capabilities of wild-type chickens, including response to conserved antigens, unique epitope coverage, and species cross- reactivity • OmniChickens generate high affinity and high specificity antibodies through CDR focused diversification
Slide 19: Acknowledgements
19 19 Acknowledgements Philip A. Leighton, Ph.D. Daniel Bedinger, Ph.D. Kimberley A. Berg Yasmina N. Abdiche, Ph.D. Jacqueline Morales Ellen J. Collarini, Ph.D. Darlene A. Pedersen Marie-Cecile van de Lavoir, Ph.D. William D. Harriman, Ph.D.