Omniab, Inc. · NASDAQ:OABI
Omniab — PEGS Europe 2023
21 slides from Omniab's conference presentation, Nov 15, 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 Phil Leighton PEGS Europe November 15, 2023
Slide 2: Single-Domain Antibodies (sdAbs)
2 Single-Domain Antibodies (sdAbs) ALSO KNOWN AS A VHH ANTIBODY OR NANOBODY® Conventional Antibody Heavy chain-only • Conventional IgG is comprised of 2 (IgG) (HcAb) heavy chains and 2 light chains • Total MW ~150kD • Binding domain is VH x VL • HcAb (found naturally in camelids) is comprised of 2 h
Slide 3: Clinical Landscape for Therapeutic sdAbs
3 Clinical Landscape for Therapeutic sdAbs ROBUST AND GROWING CLINICAL PIPELINE OF SDABS Drug name Target Therapeutic Area Phase • VHH-products comprise a Cablivi, Caplacizumab von Willebrand Factor Immune-mediated (rare blood) disorder Approved (EU 2018, US 2019) growing segment of the Ab ENWEIDA,
Slide 4: Chicken Platforms: Powered by Evolution
4 Chicken Platforms: Powered by Evolution GREATER EVOLUTIONARY DISTANCE YIELDS GREATER IMMUNOGENICITY AND MORE ANTIBODY DIVERSITY PRIMORDIAL TARGET GENE HUMAN ORTHOLOGUE MAMMALIAN LINEAGE Early form of gene prior to avian/mammalian 300 MILLION ~95 MILLION evolutionary split YEARS AGO YEARS AGO MURIN
Slide 5: OmnidAb Platform: sdAb VH and tLC Transgenes
5 OmnidAb Platform: sdAb VH and tLC Transgenes HUMAN VH3-23 WITH 10 STABILIZING MUTATIONS IN THE FRAMEWORKS VH3-23*04 CDR1 CDR2 CDR3 OmnidAb-VH Genotype: OmnidAb-VH Genotype: OmnidAb-VH Truncated Light Chain IgL KO Birds express VH but no VL tLC Spliced to WT chicken heavy chain constant region
Slide 6: OmnidAb Pseudogene Array: Diversity Through Gene Conversion
6 OmnidAb Pseudogene Array: Diversity Through Gene Conversion STABILIZED FRAMEWORKS, CDR DIVERSITY Stabilizing mutations CDR1* CDR2* CDR3** maintained in FRs *From human VH3 germline genes **From human VH3 somatic sequences OmnidAb- OmnidAb-VH pseudogenes VH Cµ Cα Cy etc. 18 17 16 15
Slide 7: B Cell Development in OmnidAb Chickens
7 B Cell Development in OmnidAb Chickens Bu-1 IgM mAb IgL IgM poly OmnidAb-VH TCR2/3 Wild type OmnidAb CH1-deletion: • No IgL • IgM epitope is in CH1 Robust B cell development in OmnidAb chickens
Slide 8: Immunizations
8 Immunizations THREE COHORTS: NKP46, TIGIT+PGRN COCKTAIL, KV1.3 TIGIT NKp46 Kv1.3 PGRN Nanodiscs Immunogen Protein Protein DNA RNA sdAb/IgL-/- 1 bird 1 bird 6 birds sdAb/tLC 2 birds 3 birds 7 birds 2-3 boosts (4-5 injections) (in process)
Slide 9: NGS: Diversity increases upon immunization
9 NGS: Diversity increases upon immunization Bird ID: 72766 72767 72773 72776 72806 72809 72847 Naïve # uniq seq: 19323 25764 14061 6565 9948 8855 17094 PBMC # lineage: 176 50 163 247 315 500 45 Immunized # uniq seq: 35240 23160 35890 30810 17693 29436 17551 splenocyte # lineage: 1270 2099 3490 5190
Slide 10: OmnidAb Birds Raise Robust, Specific Immune Responses
10 OmnidAb Birds Raise Robust, Specific Immune Responses NKp46-immunized TIGIT/PGRN-immunized
Slide 11: OmnidAb sdAbs are Antigen-Specific
11 OmnidAb sdAbs are Antigen-Specific 96w plate of sdAb-huFc supernatants (bird 72776), binding either to TIGIT or Progranulin: Yield: 0.2 – 1 mg/ml sdAb-huFc TIGIT Progranulin The way the GEMs were screened we could get either TIGIT or PGRN binders, serving as controls for each other in the ELISA
Slide 12: Specific Cell Binding to NKp46-Expressing Cells
12 Specific Cell Binding to NKp46-Expressing Cells Representative OmnidAb clone 70506p1.1.F11 in flow cytometry: Most clones show specific binding: NKp46 expressing cells Parental cells staining in dilution series no staining
Slide 13: Mutational Levels in Cloned sdAbs
13 Mutational Levels in Cloned sdAbs DATA FROM PGRN, TIGIT AND NKP46 CLONES. N = 62 FR2 * Stabilizing mutations More change of FR2 stabilizing mutations than others, in particular V37 and W47
Slide 14: OmnidAb sdAbs Have High Affinity
14 OmnidAb sdAbs Have High Affinity 70570 Number of clones 14 Number tested (some dups) 83 KD: 1.6 nM Minimum 5 nM Minimum 0.08 nM Maximum 261 nM Maximum 500 nM Median 48 nM Median 23 nM
Slide 15: Clonotypes for PGRN are Diverse
15 Clonotypes for PGRN are Diverse Sequence relatedness at protein level over entire VH domain of 30 unique anti-PGRN sdAbs
Slide 16: Binning Results on NKp46
Binning Results on NKp46 16 OmnidAb N=14 OmniFlic N=21 OmnidAb epitope coverage is distinct from that of rat on model antigen NKp46
Slide 17: Developability Assessment
17 Developability Assessment PHYSICAL PROPERTY CHARACTERIZATION OF NKP46 DAB PANEL Tm > 65°C Tagg > Tm OmnidAb clones meet ”clinical grade” developability criteria
Slide 18: OmnidAb sdAbs Show No Self-Association
18 OmnidAb sdAbs Show No Self-Association AC-SINS CHARACTERIZATION OF PGRN DAB PANEL Clinical failures FDA-approved Abs or OmnidAb™ sdAbs sdAbs Format: sdAb-huFc
Slide 19: Sequence of Non-Germline Framework Positions
19 Sequence of Non-Germline Framework Positions POTENTIAL FOR IMMUNOGENICITY OmnidAb vs. other clinical-stage molecules: CDR1 CDR2 CDR3 OmnidAb OmnidAb is designed to capture ideal attributes of clinical molecules, bypassing need for extensive in vitro engineering
Slide 20: Summary
20 Summary OmnidAb birds: • Express an optimized single domain humanized framework • No non-canonical cysteines or PTM liabilities • Produce robust titers upon immunization • Develop diverse repertoires of sdAb VH sequences • Target distinct epitopes • Produce high-affinity, antigen-specific sdAbs w
Slide 21: THANK YOU! Visit us at Booth #200
21 THANK YOU! Visit us at Booth # 200 www.OmniAb.com