AbCellera Results Presentation Deck slide image

AbCellera Results Presentation Deck

Q1 2023 BUSINESS UPDATE COPYRIGHT © ABCELLERA 6 TECHNOLOGY DEVELOPMENT. T-Cell Engager Platform Create T-cell engagers with optimal properties, fast. AbCellera THE PROBLEM Most T-cell engagers are built from sub-optimal CD3-binders CD3 I-onangages have the potential to be powerful conser treatments, but the small number of available bodies and limited multispecific anging techninkages have been tr 003-binding dovelopmors. Approximately of 1-sell engage in cinical trials an ornered with CD3-binding antibodies derived from 934-2, moustibody discovered in 1985 that is an unstrotrod Encar optopo on the N-tominus of CD3² 334-2 and the CD3-bindshx OK13 and LOTI are often heavily onginoord te moduse the rek of cytokine rolyndrome and to improve developability properti THE GOAL Build optimal T-cell engagers from novel CD3-binding antibodies Identifying-lengejers the balancu unti-tumarponcy with ples, such a cycki syndremo, requires simultaneous tuning of both the CD3 and tumor-binding arms. Pairs of antibodies that co this balansoare ram amotinga need for diverse and developable ontbodies that can be combined and tested city optimal dinio candidat To suaming Tallussapor dovolocmon wo discovered and characted novel C133-binding and with binding and functional proportos that are distings from commonly 3-4-2 To validato our CD3-binding ontbodios, wo ased our baccagneering platform, OrthoMab, to get proof-at-connes 1-el garretting the EGR an PEMA We then orgured tumor coll killing and yun resproflex in benchmark-duived alculus a difforon tumor collinos THE OUTCOME T-cell engagers with high potency and low cytokine release Wo used our high-throughput Teoll osagarplatform in chanseri ho mauting bispaanbodian The results demonst that: Tool engagers enginoored fom AbColon's portfolio da cua-binding funcional pressuperior to bo kmalculac OrthoMabanginsemd 1-aallangage favorable developability and PK properties The opamal CD3-binder depends on several tootom including tumor target ond carpet doty Together, these studies ilustrate that combining novel CD3-binding antibodies, clinically validated muticacific engineering technologies, and an integrated discovery and development in streamlines identification of optimal T-cell engagors for diverse tumor targets. Identifying T-cell engagers with optimal potency & cytokine release profiles with differentiated and developable CD3-binding antibodies T-cell engagers with optimal functional properties We generated proof-of-concept T-cell engagers with high potency and low cytokine release. Tn to sinist Maman ng T We identified T-cell engagers with optimal functional profiles. ABCallera CDS-1 CO Figure 1. T-cell engagere enginoored using diverse CD3-binding antibodies have broad tumor coll killing and cytokine release profiles. Wo generated bitcoin with a fund ifli binding sem (mama) and varied Cli-binding armas Colors discovame or Surat-darved usy our 10 cele mai nema of the cambodies Potency EC) is the concentration al ach trapecie antibody needed to incluces 50% at the masmal I calkmadiate ding of Hela col GOOD M 2. Funct Agrand C3-binting in ACCO3-2 al properties of all angagars engineered w TELAN sydd Dam LALA OrthoMab™ ongineered bispocifics with favorable developability properties. -association Polypty EMELISA SP34-CD3 hindist anodien malacuise Rambodies ongorod using a food EGFR-binding um matarunab) and 3-2) or posatuzumab (SP34-derived) using the assay described in Figum 1 2500 Figura 3. Most OrthoMabangineered bispecifics have developability properties comparable to parental antibodies. The fractional porcentage of carroty pairod vs. incorrectly pairod bispocifics was measured by intoot masa sonotremory (MS). Stability, monomariain self-association, and polyapacity were maand by 09, SEC, AC-SINS. and BVP-ELISA, respectively. CD3 T-cell engager ThCNEER-Omakam Isla 152: (0X3-1 am - Figure 4. An amplary CD3x EQFR bispecific antibody with favorable PK properties. Following a single me/kedonsin 1632 mico (humon felln tragic,), concuntrations were quantified using an electrochemluminosoene Custom-built for different tumor targets We identified optimal CD3-binding arms for different tumor targets. Toallangagar function across different timor targets and target densition Tumor target 0 3 OPE S S S S and D From novel CD3-binding antibodies Fully human CD3-binding antibodies that are distinct from commonly used molecules. Antibay querce diversity overed with aptope data AUTRES humbiasn{Meant Mar Rurca Caltent Antiry Dawnerkith frame Kang OFW Wa Valentine de Puyroiment. Lauren Cord & Che Hans Peter, super me Setaco, Pind Man Courtorial P Char, Chin, Steve Rath, AmyCH A G SK Man, Sun, Aanan Ya Rush Da Tim M, fu Tundan, Bryan C. Darhart antar NOTHERS AFFILIATION Vo La Figure 7. High-throughpat accocement of binding properties realed diverse binding Kinetics and specificities. (A) Binding affinity 10 human 3 ry and no subunts we assum by SP-coupl B E 89 Novel CD3-binding antibodies with diverse binding properties Amage of on and off retse a co Grondbindinga ✔ Leve (3) On and offered by SP- kiros and are plotted along the X and Yaxos with afinitios displayed diagonally CETATS- Figure 5. The optimal CD3-binding arm in dependent on tumor target and target donaity We compared this functions prates of CD3x PSMA and CDS EQFHI-ollungators across ondineemt ning G03-binong arms from AbCall's purel (CD3-4, CD3-2, 003-3) posetustnimah, and other aftond IGF-binding ammatumab) uraft PSMAm (TNB-685) Fusalonal properties for C03 EGFR deserved in Fein Tumoreaking and aytokin mies for CD PSMA bispawam measured 18 hours and 72 sours forlowing addition of the bespecto antibodies for N and 221 til LIVE PORTER ONO # 1886 Figur B. Proprietary immunization protocols ucing humanizedmios yielded CD3-binding antibodies with diverse sequences that bind different upitapes. Anibody were divanity wwwsusing our propranary data visualination aftwars. Colum. Cutr representeres bust on V g and and Moram sonu und CDR longths. The plati colored using data from high-throughput surface plasmonanco (SPR) pilapo binning demosting that the majority of car CD3-binding and bodies bind opitupes that an distinct from all SP34-2. C TOX (C) Subur city works by high-throughput SPH and speed specificity was measured by binding to CHO celk asing other humanoryne CO2. KEY HIGHLIGHTS Fine-tune tumor cell killing and cytokine release using TCEs that are superior to commonly-used molecules
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