AbCellera Results Presentation Deck
Q1 2023 BUSINESS UPDATE
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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
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Valentine de Puyroiment. Lauren Cord & Che
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Tim M,
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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 moleculesView entire presentation