Omniab, Inc. · NASDAQ:OABI
Omniab — Technical Presentation (December 2023)
26 slides from Omniab's technical presentation, Dec 14, 2023
Slide 1: OmnidAb: Heavy Chain-Only Transgenic Chickens Produce Human Antibodies
1 OmnidAb : Heavy Chain-Only Transgenic Chickens Produce Human Antibodies with Robust Immune Repertoires and High-Affinity Binding Christine N. Vuong, PhD Antibody Engineering & Therapeutics US December 14, 2023
Slide 2: What is a Single-Domain Antibody (sdAb)?
2 What is a Single-Domain Antibody (sdAb)? ALSO KNOWN AS VHH ANTIBODIES OR NANOBODIES® Conventional antibody Heavy chain-only antibody (IgG) (HcAb) Comprised of 2 heavy chains and 2 light chains sdAb Found naturally in camelids, comprised of 2 heavy chains, no light chain VH domain of HcAb can be ex
Slide 3: sdAbs Provide Modular Building Blocks
3 sdAbs Provide Modular Building Blocks sdABs CAN BE ASSEMBLED INTO VARIOUS FORMATS TO “FIT THE BIOLOGY” OF AN APPLICATION Fc-Scaffolded Non-Scaffolded CAR-T MONOSPECIFIC * * BI/MULTI-SPECIFIC * * • Assembly into larger or custom formats unlocks versatility to “fit the biology”; also well-suited to
Slide 4: Opportunities for sdAbs in Medicine
4 Opportunities for sdAbs in Medicine Alternate routes of administration Injectable, inhalable, & oral Penetration + fast/tunable clearance Tissues and tumors Imaging + diagnostics Small size compatible with PET/CT imaging radiolabels Broad therapeutic applications Central nervous system and neurode
Slide 5: Clinical Landscape for Therapeutic sdAbs
5 Clinical Landscape for Therapeutic sdAbs ROBUST AND GROWING CLINICAL PIPELINE OF SINGLE-DOMAIN ANTIBODIES • VHH-products comprise a growing Clinical Phase Number of VHH-based Drugs segment of the Ab market Approved 4 • 4 approved VHH-based drugs Phase 3 2 • 20 VHH-based products in clinic Phase 2
Slide 6: Current Discovery Strategy for Therapeutic sdAbs
6 Current Discovery Strategy for Therapeutic sdAbs Current process requires large animal CDR1 CDR2 CDR3 camelid VHH immunization, as well as engineering - including humanization and Multiple engineering steps required (6-12 months): Humanization optimization, which adds time and Affinity Maturation
Slide 7: Chicken Platforms: Powered by Evolution
7 Chicken Platforms: Powered by Evolution GREATER EVOLUTIONARY DISTANCE YIELDS GREATER IMMUNOGENICITY AND MORE ANTIBODY DIVERSITY HUMAN ORTHOLOGUE MAMMALIAN LINEAGE PRIMORDIAL TARGET GENE Early form of gene prior to 300 MILLION ~95 MILLION YEARS AGO YEARS AGO avian/mammalian evolutionary split MURIN
Slide 8: OmnidAb Platform: Transgene Design
8 OmnidAb Platform: Transgene Design HUMAN VH3-23 WITH 10 STABILIZING MUTATIONS IN THE FRAMEWORKS VH3-23*04 CDR1 CDR2 CDR3 OmnidAb-VH OmnidAb- OmnidAb-VH pseudogenes VH C C Cy etc. 18 17 16 15
Slide 9: OmnidAb Pseudogene Array: Diversity Through Gene Conversion
9 OmnidAb Pseudogene Array: Diversity Through Gene Conversion STABILIZED FRAMEWORKS, CDR DIVERSITY Stabilizing mutations maintained in FRs CDR1* CDR2* CDR3** *From human VH3 germline genes **From human VH3 somatic sequences OmnidAb- OmnidAb-VH pseudogenes VH C C Cy etc. 18 17 16 15 Gene conversion
Slide 10: OmnidAb Platform: sdAb VH and tLC Transgenes
10 OmnidAb Platform: sdAb VH and tLC Transgenes VH3-23*04 CDR1 CDR2 CDR3 OmnidAb-VH Predicted: Observed: OmnidAb-VH OmnidAb-VH Truncated Light Chain • Birds express VH, but no VL • Spliced to WT chicken heavy CH1-deletion chain constant region (Fc) • Spontaneous CH1 deletion
Slide 11: B Cell Development in OmnidAb Chickens
11 B Cell Development in OmnidAb Chickens Bu-1 IgM mAb IgL IgM poly OmnidAb-VH TCR2/3 Wild type CH1-deletion: No IgL IgM epitope is in CH1 Robust B cell development in OmnidAb chickens
Slide 12: OmnidAb Immunizations
12 OmnidAb Immunizations THREE COHORTS: NKp46, TIGIT+PGRN COCKTAIL, Kv1.3 TIGIT NKp46 Kv1.3 PGRN Solubilized Protein Immunogen Nanodiscs Protein Protein DNA mRNA-LNP OmnidAb 3 birds 4 birds 13 birds 2-3 boosts (4-5 injections) (in process)
Slide 13: Preliminary Response Data to Kv1.3 Ion Channel
13 Preliminary Response Data to Kv1.3 Ion Channel % Homology Species to Human Chicken 76.3% Bovine 95.3% Alpaca 97.7% Mouse 96.6%
Slide 14: OmnidAb Birds Raise Robust, Specific Immune Responses
14 OmnidAb Birds Raise Robust, Specific Immune Responses NKp46-immunized TIGIT/PGRN-immunized TIGIT 72776 PI PGRN 72776 PI NKp46 72773 PI 72806 PI 4 4 72806 PI 4 72766 PI 72809 PI 72809 PI 3 72767 PI 3 3 72847 PI 72847 PI OD450 OD450 OD450 72773 FD 72776 FD 2 2 2 72776 FD 72776 PI 72766 FD 72806 FD
Slide 15: NGS: Diversity Increases Upon Immunization
15 NGS: Diversity Increases Upon Immunization Bird ID: 72766 72767 72773 72776 72806 72809 72847 # lineage: 176 50 163 247 315 500 45 Naïve PBMC # unique seq: 19323 25764 14061 6565 9948 8855 17094 # lineage: 1270 2099 3490 5190 3252 3266 604 Immunized splenocyte # unique seq: 35240 23160 35890 3081
Slide 16: Mutational Levels in Cloned sdAbs
16 Mutational Levels in Cloned sdAbs DATA FROM PGRN, TIGIT, AND NKp46 CLONES. N = 62 FR2 * Stabilizing mutations FR2 stabilizing residues change more frequently than other FR regions High sequence diversity observed in antigen-specific clones
Slide 17: OmnidAb sdAbs are Antigen-Specific
17 OmnidAb sdAbs are Antigen-Specific sdAB-huFC SUPERNATANTS BIND TO EITHER TIGIT OR PROGRANULIN sdAb-huFc TIGIT Progranulin Yield: ~1 mg/ml Antibody response is mono-specific
Slide 18: Specific Cell Binding to NKp46-Expressing Cells
18 Specific Cell Binding to NKp46-Expressing Cells Representative OmnidAb clone in flow cytometry Clones show specific binding NKp46-expressing cells Parental (no NKp46) cells staining in dilution series no staining
Slide 19: OmnidAb sdAbs Have High Affinity
19 OmnidAb sdAbs Have High Affinity 500nM 261nM 23nM 48nM 5nM 0.08nM
Slide 20: Preliminary Binning Results on NKp46
20 Preliminary Binning Results on NKp46 N=14 N=21 OmnidAb has unique epitope coverage against NKp46
Slide 21: Developability Assessment
21 Developability Assessment PHYSICAL PROPERTY CHARACTERIZATION OF NKp46 sdABs PANEL Ideal: Tm > 60°C Tagg > 60°C Our sdAbs: Tm > 65°C Tagg > Tm OmnidAb clones meet ”clinical grade” developability criteria
Slide 22: OmnidAb sdAbs Show No Self-Association
22 OmnidAb sdAbs Show No Self-Association AC-SINS CHARACTERIZATION OF PGRN sdABs PANEL Clinical failures FDA-approved: IgG or sdAb-Fc OmnidAb sdAb-Fc Format: sdAb-huFc
Slide 23: Sequence of Non-Germline Framework Positions
23 Sequence of Non-Germline Framework Positions POTENTIAL FOR IMMUNOGENICITY OmnidAb vs. other clinical-stage molecules: CDR1 CDR2 CDR3 OmnidAb OmnidAb is predicted to have low immunogenicity
Slide 24: OmnidAb transgenic chickens:
24 OmnidAb transgenic chickens: Express an optimized single domain human framework -no non-canonical cysteines Produce robust titers upon immunization and develop functionally diverse repertoires of sdAb sequences Generate high-affinity, antigen-specific mAbs that target various epitopes Exhibit fav
Slide 25: Acknowledgements to the OmniAb Team
25 Acknowledgements to the OmniAb Team: Philip Leighton Kevin Reynolds Abheepsa Gupta Marie-Cecile van de Lavoir Ellen Collarini Darlene Pedersen Robyn Cotter Dev Srivastava Sam Zeng Gerry Sann Rivera Yulei Zhang Swetha Garimalla Bill Harriman
Slide 26: THANK YOU!
26 THANK YOU! Visit us at Booth #300 OmniAb.com