Transcript the Latest Company Presentation - Mar 11

AbCheck
Combining affinity, stability, functionality & drugability
on customized antibody formats
Company Presentation
March - 2011
1
Profile
AbCheck utilises three synergistic platforms for the discovery and generation of human antibodies:
Proprietary Phage Display libraries and Yeast Display of full-length IgG or novel formats
combined into the unique AbSieve technology
Highly validated proprietary Phage Display libraries ensure fast and reliable discovery of highly specific and
high affinity human antibodies for virtually every possible target protein
Track record of more than 25 successful antibody discovery projects
Three different proprietary libraries with a combined diversity of 1010 human antibodies
In-licensed Yeast Display technology allows screening of all antibody formats and improves drugability of drug
candidates
Selects improved drug candidates from a huge number of variants
Selection in the most relevant format including full-length IgGs, customer specific and novel antibody formats
Services range from antibody discovery to lead optimization
Attractive tailor-made deal structures and with no royalty obligations to its partners
2
Three paths to success
Phage Display
o
o
o
o
o
Yeast Display
Proven commercially – fast, robust and flexible
Proprietary libraries with a combined diversity of 10 10
provide a reliable source of highly specific human
antibodies
Monovalent display for isolation of high affinity
binders
Allows cell panning, selection of internalizing
antibodies, epitope-focused selections and much more
Isolated VH/VL pairs constitute “binding units” and can
be used in every antibody format from IgG to customer
specific and novel formats
o
o
o
o
o
Displays functional full length IgGs , tandem scFvs ,
scFvs and in all probability new customer specific and
novel antibody formats
Eukaryotic ER proof reading mechanism selects-out
misfolded antibodies
Display efficiency correlates with expression yields and
stabilities of soluble antibodies
Highest level of control by real-time, quantitative
selection of antibody clones by FACS
Enables antibody engineering in the relevant antibody
format
AbSieve
•
Yeast Display of enriched AbCheck phage display libraries in two to three panning rounds
•
•
•
Batch recloning of enriched pool
Yeast Display and FACS-based selection in the most relevant format
Expression of soluble antibodies - including full length IgGs - enables direct screening for functionality
•
Apply to existing antibodies for improvement in affinity, expression, stability and functionality
3
AbCheck Workflow - Overview
4
AbSieve: Combined strength of Phage and Yeast display
5
AbSieve: Increased probability of antibody success
AbSieve combines the strength of highly validated phage
display libraries with the advanced possibilities of yeast
display to address antibody specifications beyond affinity.
Ready-to-use and highly validated phage display libraries with
1010 different molecules are optimal tools to discover new
antibodies in minimal time.
Monovalent display on the phage allows selection of highaffinity antibodies to monomeric, dimeric or oligomeric
soluble targets or targets in their native environment on the
cell surface.
Significantly increased probability of
reaching market by identifying antibodies
to exact specifications
Improved drugability through yeast display, selecting for
enhanced soluble expression levels and stability of
antibodies.
The yeast proof reading mechanism guarantees expressability
in eukaryotic systems.
Yeast Display in combination with FACS allows real-time
monitoring and full control of the selection process.
Screening in the final drug format avoids any drop outs
caused by changes in the format.
6
Proprietary Libraries
AbCheck uses three validated distinct human libraries
Natural library derived from immune system’s antibody gene repertoire Further info
Fully synthetic library Further Info
Semi-synthetic library combining aspects of both natural and synthetic antibody libraries
Comprising a total of about 1010 sequentially and structurally diverse antibodies.
Further info
Advantages
Higher probability of isolating very specific human antibodies against every target
High diversity; approximately 1010 not only in sequence, but also in structural diversity
Antibodies tuned to best target specific properties
Validation
Track record of more than 25 successful antibody discovery projects
More than 10 antibodies from AbCheck libraries in pre-clinical programs, one in the clinic
Outstanding screening expertise including:
Several complex cell surface receptors as well as GPCR
Subnanomolar affinities
Extreme specificities
7
Library validation + panning procedure
Affinities
Monovalent binding affinities within the low
nanomolar region obtained from primary screens
Low koff rates even for monovalent scFv
Transfer into bivalent IgG usually increases binding
strength by orders of magnitude
Several means of affinity maturation can be
applied to enhance the affinity even further
8
Library validation + panning procedure
Extreme Specificities
Efficient counter-selection strategies were successfully applied to isolate antibodies with extreme
specificities:
Isoform specific antibodies:
We have isolated an antibody to the Fcg receptor CD16A (FcgRIIIa) that does not bind the
CD16B isoform despite 96% sequence identity between the two isoforms.
Specific binding to deletion mutants without binding to the wild type protein:
Specific targeting of deletion mutants is challenging, because the only unique epitope is at
the fusion site of the fragments upstream and downstream of the deleted part.
Conformation-specific antibodies:
By depleting the libraries of binders to the non-activated platelet receptor GPIIb/IIIa we were
able to isolate antibodies to the activated form of the receptor.
9
Library validation + panning procedure
Functionality
Most of the therapeutic applications require not only binding of the antibody but depend on
agonistic or antagonistic activity. From our libraries we have isolated antibodies with different
functions beyond binding:
Agonistic antibodies:
Binding of the anti CD16A antibody to the receptor activates NK cells and is very efficient in
inducing ADCC.
Blocking antibodies:
The isolated anti GPIIb/IIIa antibody inhibits binding of fibrinogen to activated thrombocytes.
Antagonistic antibodies:
We have isolated an anti IL13R antibody that interrupts the IL13 signalling cascade.
10
Library validation + panning procedure
Diversity
Our libraries have a combined complexity of 1010 antibodies. In the natural library all VH and VL
families are included giving the maximal possible structural diversity. The synthetic library
extends the diversity beyond the limits of naturally occurring antibody sequences. A
combination of natural and synthetic diversity proved in further increasing the diversity.
In a typical project 5 to 10 different
antibodies meet the requested
specifications.
11
Our Discovery Capabilities
De novo isolation of antibodies
Characterisation
Phage Display
Ready-to-use highly
validated phage display
libraries
Strong experience in
panning strategies
including cell panning
Affinity and specificity
ELISA & flow cytometry titrations
Biacore
AbSieve
Change to final drug
format during the selection
process
FACS-based selections
In vitro functionality
Target specific cell-based assays
Stability
Assessed in thermofluor assays
Lead Optimisation
Phage or Yeast Display
Sublibraries for lead
optimisation can be
created for phage or yeast
display
Addressing
Affinity, expression levels,
stability and functionality
Possible in different
antibody formats
Yeast Display platform
allows lead optimisation of
IgGs or other antibody
formats
12
Partner Benefits
Three discovery platforms ensure three paths to the best antibodies
AbSieve is based on highly productive and validated technologies
Drugable antibodies delivered in very competitive time frames to virtually any target
Three distinct proprietary libraries expressing about 1010 human antibodies
Significantly increased probability of identifying antibodies to exact specifications
Proven track record of isolating more than 25 different human antibodies
Strong IP position allowing flexible, tailored deal structure
No royalty obligations to third parties
Senior team with a proven track record in the discovery and research of therapeutic
antibodies
Proven, highly enabling technologies combined with attractive cost structures
13
Summary
The Human antibody discovery specialist in commercially validated yeast and phage technologies
Antibody discovery for virtually all targets in all formats
Higher probability of reaching market by screening in final antibody drug format
The unique AbSieve technology delivers drugable antibodies within highly efficient timelines
Three commercially validated diversified antibody libraries
AbCheck offers tailored deals with no royalty obligations
Thank you
14
Senior Management
Dr. Volker Lang (Managing Director)
16 years experience in the biotechnology sector, spanning basic research, industry
R&D, Business Development and Licensing, commercial operations and management
Background as scientist and project manager combined with extensive experience in
the commercialization of biotechnology products
Considerable CMC/Production experience in his previous positions as Chief Business Officer
(Affimed Therapeutics AG) and Vice President Corporate Development (Scil Technology
GmbH)
Dr. Vera Molkenthin (Chief Scientist and Head of Discovery)
Many years experience in the selection of antibodies using phage display
PhD from the Faculty of Biology in Mainz with main focus on construction of a phage
display library and the selection of stabilizing mutations
Head of Screening at Affimed with responsibility for the management of the screening
group, with special emphasis on generation of highly diverse antibody libraries, and
design and execution of the most appropriate selection procedure for a particular
target
15
Contact
Volker Lang, PhD
(Managing Director)
Phone: +420 378 05 1500
[email protected]
AbCheck s.r.o.
Vedeckotechnicky park Plzen
Teslova 3
CZ-301 00 Plzen
www.AbCheck.eu
16
Appendix
17
Natural Antibody Library
Fully human library
In vivo created diversity of antibody sequences comprising sequential as well as structural
diversity
New combinations of VH and VL chains from multiple healthy donors
No bias due to amplification of the VH chains by IgM specific priming
Special assembly technology guarantees > 70% functional clones
Reliable and rapid selection of highly specific and high affinity antibodies on recombinant proteins or cells
18
Back to Libraries
Fully Synthetic Library
Synthetic library
Generated by introducing randomized sequences in the antibody binding site of
selected frameworks
Ensuring reliable folding and high expression yields
Diversity generated in vitro thereby
Avoiding counter selection against anti-self antibodies
19
Back to Libraries
Semi-Synthetic Library
Semi-synthetic library
Combining the advantages of the natural and synthetic library
Diversity and reliable folding and high expression
Increasing the diversity of binding molecules even further
20
Back to Libraries
Yeast Display Explained:
The following four slides define the yeast display library AbCheck utilises
for antibody discovery
TM
SECANT platform is the proprietary technology of Celexion LLC
21
SECANT™ Platform Overview
• The SECANT™ platform is a next-generation antibody display system that can
handle large and complex proteins
• First yeast system to display full-length IgG antibodies
• Proven to display tandem scFv, bispecific and proprietary scaffolds
• Enables high throughput assay of 108 to 109 variants for
• De Novo Antibody Discovery
• Complex Scaffold Engineering
• Scaffold Reformatting
• Affinity Maturation
• Stability/Solubility/Folding Control
• Humanization
• The SECANT™ platform will accelerate discovery timelines by allowing faster
characterization and higher throughput
• SECANT™ platform is compatible with many types of proteins and libraries
• Full length IgG and scFv, fibronectin, receptor ectodomains, superoxide dismutase,
human serum albumin, vitamin D-binding protein
Source: Celexion
22
SECretion and CApture Tech. (SECANT™)
1. The gene for the variant protein to be
engineered (the “gene of interest“) is
expressed as a fusion to a biotin acceptor
peptide (BAP). A co-expressed biotin
ligase attaches biotin to the BAP tag on
the expressed protein.
Source: Celexion
2. Avidin is attached to the outer wall of
the host cell.
SECANT™ platform (continued)
3. The biotinylated protein of interest is
secreted into the extracellular space
where it binds to the surface-localized
avidin. Approximately 105 proteins can be
captured on the yeast surface in this
manner.
Source: Celexion
4. The captured proteins can be assayed
for binding, expression, or enzymatic
activity by labeling with a fluorophoretagged ligand, antibody, or substrate.
Protein functionality can then be assayed
and the best clones isolated by FACS.
SECANT™ platform can display
functional, full-length IgG
Source: Celexion