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The biologics market is being driven by innovation in design and diversity of biologic molecules. Directed evolution of biologics is critical to generating and screening an array of novel constructs for the right activity and properties. This conference
will provide a review of the newest tools essential for antibody engineering. Leaders in the field will showcase the latest trends in technologies and approaches for creating the next generation of drug candidates.
MONDAY, MAY 4
7:00 am Registration and Morning Coffee
Plenary Keynote Session
8:30 Chairperson’s Opening Plenary Remarks
8:40 Cancer Stem Cells and Mechanisms of Malignant Progression
Robert A. Weinberg, Ph.D., Founding Member, Whitehead Institute for Biomedical Research; Professor,
Biology, Massachusetts Institute of Technology
The cell-biological program termed the epithelial-mesenchymal transition (EMT) plays a role in conferring aggressive traits on carcinoma cells. In addition, it generates cancer stem cells (CSCs) that have the ability, following dissemination, to serve
as founders of new metastatic colonies. The relationship between these CSCs and the SCs residing in normal tissues, and the participation of the CSCs in metastatic dissemination will be described.
9:25 Building an Antibody Discovery Company in a Crowded Field – the Adimab Story
Tillman Gerngross, Ph.D., CEO, Co-Founder, Adimab
The presentation will cover the evolution of Adimab from its founding in 2007 to becoming one of the few privately held profitable biotech companies in the last decade. Industry trends and specific strategic decisions along the way will be discussed
and used to illustrate the importance of integrating finance and scientific information to build successful capital efficient biotech companies.
10:10 Coffee Break
10:45 Chairperson’s Remarks
Gregory A. Weiss, Ph.D., Professor, Chemistry, Molecular Biology & Biochemistry, University of California, Irvine
KEYNOTE PRESENTATIONS
10 :50 Biophysical Properties of Antibody Drugs: Predicting and Engineering Developability
K. Dane Wittrup, Ph.D., C.P. Dubbs Professor, Chemical Engineering & Biological Engineering; Associate Director,
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology
The field of antibody engineering has evolved from simply plucking binders out of libraries to engineering molecules with industrial-grade expression, stability, solubility, and specificity. For small molecules, the “Lipinski Rule of 5”
provides a widely accepted rule of thumb for structural features consistent with successful drug development. Is there a similar pattern in the values for biophysical properties of developable antibody drugs? Analysis of a broad spectrum of features
of a large sample of antibodies in commercial clinical development will be presented with an eye towards the emergence of such criteria for antibodies.
11:20 The Rise of Bispecific Antibodies as Therapeutics
Paul J. Carter, Ph.D., Staff Scientist and Senior Director, Antibody Engineering, Genentech, Inc.
Bispecific antibodies are coming of age as therapeutics with 1 bispecific antibody approved and over 20 more in clinical development. This presentation will discuss alternative technologies for the efficient production of bispecific antibodies including
bispecific IgG plus potential therapeutic applications.
11:50 Novel Affinity and Targeting Tools for Life Sciences
Paul Ko Ferrigno, Ph.D., CSO, Avacta Life Sciences
Affimers are engineered affinity proteins that are suitable for a range of applications. We will introduce Affimers in applications traditionally dominated by antibodies before focussing on two novel applications. First, inhibition of protein interactions
in cells. And, secondly, development of a novel protein microarray. This has driven establishment of a HTP protein expression pipeline capable of producing > 4000 Affimers a week, allowing production of high complexity Affimer microarrays,
which are being used for biomarker discovery.
12:20 pm Luncheon Presentation I: Antibody Library Display on a Mammalian Virus: Combining the Advantages of Panning and Cell Sorting in One Technology
Ernest S. Smith, Ph.D., Senior Vice President, Research & Chief Scientific Officer, Vaccinex, Inc.
We have developed an antibody discovery platform that enables efficient mammalian cell-based expression of a library of human antibodies in full length IgG format on the surface of a mammalian virus. Upon infection of mammalian cells the antibody
is not only incorporated into the newly produced virus, it is also displayed on the surface of the host cell. This technology allows us to combine the advantages of virus panning and cell sorting into one technology.
12:50 Session Break
1:50 Chairperson’s Remarks
Aaron K. Sato, Ph.D., Vice President of Research, Sutro Biopharma
1:55 Construction and Use of Large Antibody Libraries in Mammalian Cells
John McCafferty, Ph.D., CEO and Founder, IONTAS Ltd.
Using nuclease-directed integration of antibody genes we have constructed large libraries in mammalian cells containing a single antibody gene/cell. This allows surface display of antibodies, including IgG formatted antibodies, on the cell surface.
This will permit the screening of millions of clones by flow sorting and provide information on both expression level and the extent of binding within the cell types used for antibody production.
2:25 Engineering Cow Ultra-Long CDR3 Antibodies
Vaughn Smider, M.D., Ph.D., Assistant Professor, Cell & Molecular Biology, Scripps Research Institute
Cows have ultralong CDR H3s which can have lengths of nearly 70 amino acids and form a novel b-ribbon “stalk” and disulfide-bonded “knob” structure that protrudes far from the canonical antibody paratope. We have engineered
cow antibodies for binding and inhibiting an ion channel at high potency, and have humanized the scaffold for potential therapeutic use.
2:55 Phage Selection of Light-Responsive Ligands
Christian Heinis, Ph.D., Professor, Institute of Chemical Sciences and Engineering (ISIC), Ecole Polytechnique Federale
de Lausanne (EPFL)
Peptide libraries encoded by phage display can be modified in chemical reactions to extend their chemical and structural diversity. Well established is the method to cyclize peptides on phage to generate bicyclic peptide ligands. Recently, we
have chemically modified phage peptide libraries with an azobenzene moiety in order to evolve light-responsive ligands. The approach and properties of the isolated photoswitchable peptides will be presented.
3:25 Towards a New Class of Bio-Therapeutics based on Synthetic Genetic Polymers
Philipp Holliger, Ph.D., MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus
I’ll present recent work on the discovery of novel aptamer ligands directed against a viral RNA and a protein target and composed entirely from an unnatural nucleic acid architecture that is completely resistant to degradation by serum nucleases
and withstands prolonged exposure to acid without loss of structure or activity. I’ll discuss the prospects of this technology to provide a new class of biotherapeutics based on an expanding range of evolvable synthetic genetic polymers.
3:55 Refreshment Break in the Exhibit Hall with Poster Viewing
4:35 Human Antibody Phage Libraries with Elongated VH CDR3 Loops
David Lowe, Ph.D., Director, R&D, Antibody Discovery and Protein Engineering, MedImmune Ltd.
Antibodies with longer (> 15 amino acids) VH CDR3 loops are naturally present in humans at low levels. Reports have suggested that they play a useful role in, for instance, viral neutralisation. Here we report on the design, construction
and assessment of a novel phage display library of human antibodies with designed elongated VH CDR3 loops.
5:05 Optimizing Antibody Expression by Using the Naturally Occurring Framework Diversity in a Live Bacterial Antibody Display System
Christoph Spiess, Ph.D., Scientist, Antibody Engineering, Genentech
Rapid identification of residues that influence functional expression and stability of poorly behaved antibodies is often needed to move promising therapeutics into the clinic. To establish a method that can assess small expression differences,
we developed a Bacterial Antibody Display system that overcomes previous limitations, enabling the use of full-length formats for antibody and antigen in a live cell setting. We designed a novel library of individual framework variants
using natural diversity, and screened for increased expression. We successfully identify variants that dramatically improve yields and thermodynamic stability of two therapeutic antibodies in E. coli and mammalian cells. Our natural library
design strategy could be applied during antibody humanization and library design for in vitro display methods to maintain expression and stability.
5:35 Welcome Reception in the Exhibit Hall with Poster Viewing
6:50 End of Day
TUESDAY, MAY 5
8:00 am Morning Coffee
8:25 Chairperson’s Remarks
Gregory A. Weiss, Ph.D., Professor, Chemistry, Molecular Biology & Biochemistry, University of California, Irvine
8:30 Amplified Signal Generation from Phage-Based Protein Sensors
Jennifer N. Cha, Ph.D., Norviel Associate Professor, Chemical and Biological Engineering, University of Colorado,
Boulder
The first part of the talk will describe our use of a dually-modified version of filamentous bacteriophage that produces significantly higher colorimetric signals than what can be achieved using antibodies alone. The second half of the talk
will highlight our recent efforts of using the genetic information of the M13 bacteriophage to generate highly amplifiable signals in a single solution isothermally.
9:00 Mining for Tumor Targeting Peptides: New Ligands for Molecular Imaging & Personalized Therapies
Kathlynn C. Brown, Ph.D., Program Director, Center for Chemical Biology, SRI International
Tumor targeting ligands are emerging components in cancer therapies. Widespread use of targeted therapies and molecular imaging depends on increasing the number of tumor-specific ligands. Biopanning of phage-displayed peptide libraries on
a series of non-small cell lung cancer lines provided numerous ligands with affinities and cell-specificities that rival monoclonal antibodies. Selection and use of these ligands for diagnosis, molecular imaging, and therapies will be
discussed.
9:30 Identify Macropinocytosing Antibodies by High Content Analysis of Phage Display Library Selection Output
Bin Liu, Ph.D., Professor, Anesthesia, University of California, San Francisco
The macropinocytosis pathway is capable of both rapid and bulk endocytosis, and recent studies have demonstrated that it is selectively upregulated by cancer cells. While phage antibody display libraries have been utilized to find antibodies
that bind and internalize to target cells, no methods have been described to screen for antibodies that internalize specifically via macropinocytosis. We hereby describe a novel screening strategy based on High Content Analysis to identify
novel human antibodies that enter tumor cells via macropinocytosis
10:00 Coffee Break in the Exhibit Hall with Poster Viewing
10:50 Engineering a Rationally-Identified 5 KDA Protein Scaffold for Molecular Imaging
Benjamin J. Hackel, Ph.D., Assistant Professor, Chemical Engineering and Materials Science, University of Minnesota
Using an algorithm to evaluate natural protein domains for their potential as scaffolds for molecular recognition, we developed a new 45 amino acid scaffold capable of picomolar affinity binding while retaining high thermal stability. Application
to tumor targeting for molecular imaging will be discussed.
11:20 A New High-Throughput Platform that Enables Functional Screening of Diverse Protein Libraries
Jennifer R. Cochran, Ph.D., Hitachi America Associate Professor, Bioengineering and Chemical Engineering, Stanford
University
We developed a new screening platform that allows researchers to assay the functional activity of millions of protein variants, displayed on or secreted from bacteria or yeast. This transformative technology, which is essentially a 10 million
well microtiter plate the size of a penny, has enabled a broad range of protein engineering applications, including antibody, enzyme, and biosensor engineering from bacteria or yeast libraries.
11:50 Zymogen Activator Peptides Selected by Phage Display
Robert A. Lazarus, Ph.D., Principal Scientist, Early Discovery Biochemistry, Genentech, Inc.
Serine proteases and serine protease-like domains undergo large conformational changes upon cleavage of single-chain inactive zymogens to two-chain fully active proteases. Using structure-guided peptide phage display combined with activity-based
sorting, we engineered high affinity zymogen activator peptides (ZAPtides) that selectively bind to the ‘activation pocket’, trapping zymogens in their active protease conformations based on results from biochemical, biological
and structural studies.
12:20 pm Enjoy Lunch on Your Own
1:20 Ice Cream Break in the Exhibit Hall with Poster Viewing
2:00 Chairperson’s Remarks
Andrew M. Bradbury, M.D., Ph.D., Staff Scientist, Biosciences, Los Alamos National Laboratory
2:05 Engineering Neutralizing Antibodies to Guide Vaccine Design
William R. Schief, Ph.D., Professor, Immunology & Microbial Science, Scripps
Research Institute; Director, Vaccine Design, International AIDS Vaccine Initiative
Neutralizing antibodies isolated from natural infection can serve as guides for vaccine design and as leads for therapeutics, but there are limitations to those approaches. This talk will describe our efforts to employ computational design,
yeast display directed evolution and other technologies to engineer antibodies to provide more detailed guidance for vaccine development, enabling a reductionist approach.
2:35 Synthetic Antibodies for Ebola virus Immunotherapy
Jonathan Lai, Ph.D., Associate Professor, Biochemistry, Albert Einstein College of Medicine
Synthetic antibody engineering is an emerging technology for the identification of highly specific antibodies from large molecular display libraries. Here, we will discuss our progress in application of this method to discover potential immunotherapies
for Ebolavirus infections. The ebolaviruses and Marburg virus cause severe hemorrhagic fever with human case fatality rates of up to 90%. Cocktails of monoclonal antibodies have demonstrated post-exposure efficacy in non-human primate
studies and therefore represent a promising therapeutic platform. We have identified novel synthetic antibodies against the glycoproteins of the Zaire (EBOV) and Sudan (SUDV) Ebolavirus species. These antibodies have neutralization potential
and, in the case of SUDV, afford post-exposure protection of mice from lethal viral challenge. These antibodies have significant immunotherapeutic potential and demonstrate the applicability of synthetic antibody engineering to biomedical
and public health challenges.
3:05 Combining Phage and
Yeast-Display: Discovery and Optimization of Highly Developable Antibodies
Vera Molkenthin, Ph.D., Chief Scientist, AbCheck s.r.o.
Jacob Glanville, CSO, Distributed Bio Inc.
An integrated discovery and optimization platform was established that selects for developable antibodies. Combining Phage and Yeast Display demonstrated as versatile to select dozens of IgG with good binding properties. The optimization platform
AbAccel enables affinity maturation while simultaneously addressing stability, species cross-reactivity, specificity and humanness to generate highly developable antibodies from human and non-human leads. 10-100-fold affinity improvements
have been achieved.
3:35 Refreshment Break in the Exhibit Hall with Poster Viewing
4:20 Chairperson’s Remarks
Andrew M. Bradbury, M.D., Ph.D., Staff Scientist, Biosciences, Los Alamos National Laboratory
4:25 Computer-Guided Design and Validation of Epitope-Specific Antibodies against Difficult Targets
Yanay Ofran, Ph.D., Founder, Biolojic Design Ltd.
A major challenge in Ab discovery today is the development of biologically active Abs against difficult targets. We introduce a computer-guided platform that generates fully-human high affinity Abs against pre-selected epitopes on virtually
any target. The platform allows efficient and rapid design of Abs against GPCRs and ion channel, species cross reactive Abs, bispecific Abs, and Abs against cryptic epitopes.
4:55 Design and Use of Hyperstable Synthetic Human Antibody Libraries
Pierre Martineau, Ph.D., Group Leader, IRCM, INSERM
The design of synthetic antibody libraries requires making choices: Choosing the right framework(s), where and how to introduce the diversity, best antibody format, optimizing expression levels. We will discuss the construction and the use
of two generations of our hyperstable antibody library made in the group. We will exemplify particularly the links between design rules and the planed applications of the antibodies as intrabodies.
5:25 End of Conference
5:30 Registration for Dinner Short Courses