AbCellera Results Presentation Deck

Q1 2023 BUSINESS UPDATE COPYRIGHT © ABCELLERA 7 TECHNOLOGY DEVELOPMENT. T-Cell Engager Platform Unlock high-value, difficult cancer targets. THE OPPORTUNITY AbCellera Unlock intracellular tumor targets immunotherapies are transforming cancer treatment by moting the immune system to right cancer. T-cat engagers-a type of immunotherapy-etminste cancer ces by simultaneously binding tumor targets and the T-cell acting protein CD3. Because T-cell engagers cannot socess intracellular targets, their use is limited to targets expressed on the tumor cell surface. Toel engages against peptides oisplayed on major ristocompaticity complexes (MHCS) are proming approach for unlocking previously inaccessible, high-valce. intracellular tumor targets, One such target is metanema associated antigen 4 PMHC (MAGE-44-0MHC), a tumor-specinc antigen expressed by many did tumors, but not by most healthy. THE CHALLENGE Finding rare antibodies against pMHCS MAGE-44-MHCs are challenging immunotherapy targets because (a) proteins within the MAGE-A family are highly homologoue (MAGE A4 is often mutated in tumor cells and there is very low expression of MAGEM OMHO on tumor Antibodies that bind to MAGE-44-MHC with the specificity ond affinity needed to minimize the risk of off-target binding are rare. Those that do bind and have favorable developably profiles are even more rare, making them acut to identity using traditional approaches Furthermore, Toll engager development requires tumor-binding antibodies that function assispecies, creating a need for diverse antibodies that can be paired with CDS-binders and tested for optimal function THE SOLUTION Start with diverse panels of pMHC-binding antibodies. We used our and body discovery and development engine to discover and one MAGE 44 binding antibodies with favorable binding and developablity profes terite huNG L LeadMAGE-AS-RHC arbodies will be selected and paired with our panel of previously described CDS-binding antibodies using our sispecific engineering platform. THE OUTCOME OrthoMa", to streamline the development of MAGE A4 MHC Telenders. We identified a panel of antibodies against MAGE-A4-pMHC with: ☐ diverse sequence and binding profes t-specific, high-offinity binding favorable developability profes Breaking barriers to access intracellular targets with T-cell engagers Discovery of diverse, developable, and ultra-specific antibodies against a MAGE-A4 pMHC 45 diverse antibodies against a MAGE-A4 peptide-MHC target Antody discovery 1.5M se Single-cell screening Mbada acaring any k 466 200 45 de Figure 1. Propriotary immunication technologies and high-throughput semning strategis used to writy and captum wahedy diversity (A) Hum were immuned with human phAGE-A presered on MHC-HLA02-01) (Bu baad-besed single-oal soaring assays were used to sees 1.5 milion single Bells and identity antibodies that bind to MAGE-A4, but not MAGE-02-0 BARS-VHC anslated peptide control (C) 45 MAGE-A4-MHC-binding from 23 cofres with secance deity was selected for high-throughou bodies expression and further characterization SUK Ow CYPAR VPS130 Ultra-specific, high-affinity MAGE-A4-pMHC binders Expanded peptido panel for hinding assessmen y RAM NMP TSPANS Sequence diversity Trouser VYA CHET indeva gras sprassin Figure 3. MAGE A4-MHC-binding antiboches a highly apsodio. (1) Antibody binding was further unga high-throughput peptide-pubed 12 way with MAGE-AAC and 13 other related pHC, including seven pHCG from the MAGE protein fomly one 13 MHC generated using the Selective Coes-Reactive Artgen Preton (RA) algorith. Practed indig ates of de to M-Csere calculated using Co. Rate MHC- levels in 12 colspused with different packs samasure of positive peptide binding 0 MHC-0 are shown, Peptides marked with were escladed due to week peotide-MHC-binding Qualitative binding met Ending kin Ⓒ MADEM MARE CHEL sro Col-binding assent P SARK Fe 2. MACE-A4-MHC-binding antibodies were identified (A) Ansbody binding was assessed using a multiplesed bead-besed binding validation assay with MAGE-A4-pHC and closely related MHCnding (>5F0D como MAGE-A4-MHC binding benchmark ort body and detected using flow cytometry Sensorgrams generated from Surface Plasmon Resonance (SPR kans of a selected target-binding asoodyshowtively strong binding to MNGE MHC compared to MAGE 48-CMHC No binding was observed to MAGE-83- or SARS-MO MMC 1 (8) High MAGE-MaMHC binding and bod en show high opty for MAGE A4 HC with low tone binding to the other posted Pepada panel for binding ment GRYPARENTY Oran PO PASTRECTH Binding affinity ⒸSPR FO Wil (C) body binding was further assessed in a Desde pused T2 with MAGE-A4-MC and closel edding 5 FOD was detected using tow Over 70% of antibodiested bound to both MAGE-A-HC and MAGE AD OMHC a closely related pepe expressed on tumor cells in both De y MHC- genopression lavals in 12 cella pulsed with forent optides (as a measure of povepose binding to MHC-ase show 101 (C) Senetic analysis of antibody binding to MAGE A4 CandMAGE ABMHC No anding was observed to M82 or SARS HO not shown Biophysical assem ICE 505 300 Developable antibodies with favorable biophysical properties En palam 200 AUTHORS Ce Toronto Bergant Tim Jacob Groce Lounge Vigo Antos Sarka, Harveer Chap We Shirley de Sal Gocean. Cindy Los Crichten Mal Ciel, Jessic Permende deure Kord A La Massene under Ar Conclusions & next steps REFERENCES F 100 min Wensbody diecosery and development ong nowo dod panel of diverse and develoosble antibodies that bind with high af affinity and high specificity to by recoma are specific for MAGE-44 o mation other pack that bind to MHC-with highatty have table developby 2 200 Body making Figure 4. MAGE-A4-MHC-binding antibodies have favoble developability profiles with high t med by capary gel electrophore using adum dadecyl CE-SDS), or aggregation med by absolute size exclusion chromatography 05 low relative surface drophobicity mesured by anatical hydrophobic interaction chromatography (C) high stability med brynars differentialing Buatry, low polyspecificity axed by baculovirus particle ayme-inkedimenty EVP-EUSAL and low oelf-association measured by offinit capture self-interactionnanosarticle spect (AC-SINS) with cores normalized to high and low controls LOG # 1891 POST APCSO CS Thats wilhe pared with our pr described fully human CD-binders to get Tell engagors for further dovolent. We w Sinfunctional devlopaty and specificity assays including tumor celling and cata biecificantibody develouably essensents deed 12 lainding with degradating thay apel of pain anon-sto Investigate potential off-laget closer high-resolution structural assessments of and body-Cin KEY HIGHLIGHTS Find ultra specific antibodies that are comparable or superior to clinical benchmarks

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