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Antibody discovery solutions for research, diagnostic and therapeutic goals Banishree Saha*, Valeria Busygina*, Jamie Campbell, Jacinto Villanueva, Jayne Hammersley, Dele Ashiru, Reem Mahrat, Jennifer Alleman-Sposeto, Yani Chen, Emily Kossa, Joyce Young Abcam plc, Discovery Drive, Cambridge Biomedical Campus, Cambridge, CB2 0AX, UK Supporting antibody discovery: research to commercialization From Spleen via clonal Hybridoma to recombinant RabMAb ® : BCMA Next generation sequencing (NGS) based antibody selection RabMAb® antibodies via hybridoma Specific: Proven success for generating specific antibodies to point mutations or PTMs Sensitive: High affinity antibodies without polyclonal variability Pair performance: Proven performance of antibody pairs in immunoassays Next Generation Sequencing-based antibody selection 10-100 fold increase in the number of antibody clones for evaluation Support IP portfolio through variant lineage analysis Insight into the complete antigenic response AxioMx phage display antibody discovery Speed: ~6 month binder generation Antibody engineering: affinity maturation, CDR grafting, antibody framework optimization Toxic antigens: animal-free system to generate binders to toxins RabMAb® antibodies via peripheral B-cell cloning Speed: Sample early bleeds for application specificity, direct cloning from whole blood Immunostaining: Workflow optimized for IHC MAb discovery Fusion-free: Due to IP/licensing, for certain applications, fusion- free approaches may be desirable Specific approach for your unique binder Tailor-Made project design supported by expert scientific team, includes: challenging targets assay support diverse applications Collaborative and flexible milestone-based projects with results-based progression wrap-around service & collaborative project approaches flexible licencing and commercial structures BCMA: A druggable target for multiple myeloma BCMA Promotes proliferation & survival of MM cells Associated with immunosuppressive microenvironment THERAPEUTICS CAR-T, T Cell Engagers, ADC Human/Mouse X-reactive RabMab ® identified; binds to both with sub-nM EC50 anti-BCMA RabMAb ® neutralise BAFF binding to BCMA with sub-nM IC50 -11 -10 -9 -8 -7 -6 -20 0 20 40 60 80 100 120 140 Inhibition of BAFF binding to BCMA Log/M % of max BOB-1 F1-8 BOB-1 F1-24 Rabbit IgG Bottom Top LogIC50 HillSlope IC50 BOB-1 F1-8 7.407 102.2 -9.208 -1.269 6.194e-010 BOB-1 F1-24 1.431 101.9 -9.267 -1.705 5.406e-010 From Peripheral Blood ASC direct to recombinant RabMAb ® : PDL1, PD1, CTLA4 T-cell targets for immunotherapy Completed targets Calico Biolabs Inc. Acquired January 2019 Nature. 480 (7378): 480-489. T-cell targets for immunotherapy CAL clones optimized for IHC Abcam support complimentary diagnostics needs We can provide access to RUO community for your reagent validation Diagnostics supported by our Quality systems, including ISO13485 and CFR21 Access to our strategic partnerships to develop your Dx Paired single B-cell NGS Bioinformatic analyses and sequence-based rational selection of leads Expand IP portfolio surrounding target binding through lineage variant analysis NGS allows access to entire antibody repertoire Antibody repertoire after antigen enrichment Distance from Germinal Genes (Average nucleotide changes/100 bp) Number of Unique Sequences within Lineage (Log2 Scale) CDR3 Family (Lineage) Node size proportional to lineage size Lineages recovered by fusion and NGS Lineages recovered by NGS only Comprehensive database of antigen-specific binders that can be parsed experimentally for activity Breadth of the antigenic response for binder discovery: A rational approach for antibody discovery, eliminating redundancy and maximizing diversity in epitope recognition Wide selection of candidate clones to achieve product specification Accurate VH/VL pairing by single B-cell sequencing Lineage analysis using depth and breadth

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  • Antibody discovery solutions for research, diagnostic and therapeutic goalsBanishree Saha*, Valeria Busygina*, Jamie Campbell, Jacinto Villanueva, Jayne Hammersley, Dele Ashiru, Reem Mahrat, Jennifer Alleman-Sposeto, Yani Chen, Emily Kossa, Joyce YoungAbcam plc, Discovery Drive, Cambridge Biomedical Campus, Cambridge, CB2 0AX, UK

    Supporting antibody discovery: research to commercialization

    From Spleen via clonal Hybridoma to recombinant RabMAb®: BCMA

    Next generation sequencing (NGS) based antibody selection

    RabMAb® antibodies via hybridoma

    Specific: Proven success for generating specific

    antibodies to point mutations or PTMs

    Sensitive: High affinity antibodies without polyclonal variability

    Pair performance: Provenperformance of antibody pairs in immunoassays

    Next Generation

    Sequencing-based antibody selection

    10-100 fold increase in the number of antibody clones

    for evaluation

    Support IP portfolio through variant lineage analysis

    Insight into the complete antigenic response

    AxioMx phage display antibody discovery

    Speed: ~6 month binder generation

    Antibody engineering: affinitymaturation, CDR grafting,

    antibody framework optimization

    Toxic antigens: animal-free system to generate binders to

    toxins

    RabMAb® antibodies via peripheral B-cell cloning

    Speed: Sample early bleeds for application specificity,

    direct cloning from whole blood

    Immunostaining: Workflow optimized for IHC MAbdiscovery

    Fusion-free: Due to IP/licensing,

    for certain applications, fusion-

    free approaches may be desirable

    Specific approach for your unique binder

    Tailor-Made project design supported by expert scientific team, includes:

    – challenging targets– assay support– diverse applications

    Collaborative and flexible– milestone-based projects with results-based progression– wrap-around service & collaborative project approaches– flexible licencing and commercial structures

    BCMA: A druggable target for multiple myeloma

    BCMA

    – Promotes proliferation & survival of MM cells

    – Associated with immunosuppressive microenvironment

    THERAPEUTICS

    – CAR-T, T Cell Engagers, ADC

    Human/Mouse X-reactive RabMab® identified; binds to both

    with sub-nM EC50

    anti-BCMA RabMAb® neutralise BAFF binding to BCMA with

    sub-nM IC50

    -1 1 -1 0 -9 -8 -7 -6-2 0

    0

    2 0

    4 0

    6 0

    8 0

    1 0 0

    1 2 0

    1 4 0

    In h ib it io n o f B A F F b in d in g to B C M A

    L o g /M

    % o

    f m

    ax

    B O B -1 F 1 -8

    B O B -1 F 1 -2 4

    R a b b it Ig G

    Bottom Top LogIC50 HillSlope IC50

    BOB-1 F1-8 7.407 102.2 -9.208 -1.269 6.194e-010

    BOB-1 F1-24 1.431 101.9 -9.267 -1.705 5.406e-010

    From Peripheral Blood ASC direct to recombinant RabMAb®: PDL1, PD1, CTLA4

    T-cell targets for immunotherapy

    Completed

    targets

    Calico Biolabs Inc.

    Acquired January 2019

    Nature. 480 (7378): 480-489.

    T-cell targets for immunotherapy

    CAL clones optimized for IHC

    – Abcam support complimentary diagnostics needs

    – We can provide access to RUO community for your reagent

    validation

    – Diagnostics supported by our Quality systems, including

    ISO13485 and CFR21

    – Access to our strategic partnerships to develop your Dx

    – Paired single B-cell NGS– Bioinformatic analyses and sequence-based rational selection of leads – Expand IP portfolio surrounding target binding through lineage variant analysis

    NGS allows access to entire antibody repertoire

    Antibody repertoire after antigen enrichment

    Dis

    tan

    ce

    fro

    m G

    erm

    ina

    l Ge

    ne

    s (A

    ve

    rag

    e n

    uc

    leo

    tid

    e c

    ha

    ng

    es/

    10

    0 b

    p)

    Number of Unique Sequences within Lineage (Log2 Scale)

    CDR3 Family (Lineage)

    Node size proportional to

    lineage size

    Lineages recovered by fusion and NGS

    Lineages recovered by NGS only

    Comprehensive database of antigen-specific binders

    that can be parsed experimentally for activity

    Breadth of the antigenic response for binder discovery:

    – A rational approach for antibody discovery, eliminating redundancy and maximizing diversity in

    epitope recognition

    – Wide selection of candidate clones to achieve product specification

    Accurate VH/VL pairing by single B-cell sequencing

    Lineage analysis using depth and breadth