2017 Archived Content
Phage and yeast display are the tools that allow the creation of novel antibodies and biologic drugs that are advancing into clinical development. Recent strides to engineer molecules to cross the blood brain barrier and address difficult targets such
as ion channels and membrane proteins are generating encouraging results. Employing phage for novel uses include probing the microbiome, screening intracellular targets, and understanding unique advantages of alternate phage IX to enable libraries
with improved functionality and capabilities. Deep sequencing of libraries and analysis of output offer a greater understanding of immune biology and in turn allow us to make strides in designing molecules against oncology, immunotherapy and autoimmune
disease by shedding light on why therapies fail and how we can improve them.
Scientific Advisory Board
Ana Barbas, Ph.D., Coordinator, Bayer Satellite Laboratory at iBET, iBET and Bayer Portugal SA
Kerry Chester, Ph.D., Professor, Molecular Medicine, University College London Cancer Institute
David
Lowe, Ph.D., Senior Director, R&D, Antibody Discovery and Protein Engineering, MedImmune Ltd
John McCafferty, Ph.D., Co-Founder, Director and CEO, IONTAS Ltd
Ahuva Nissim, Ph.D., Reader, Molecular Targeting, Biochemical Pharmacology,
William Harvey Research Institute, Queen Mary University of London
Final Agenda
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MONDAY 13 NOVEMBER
12:00 Registration
13:40 Welcome from PEGS Europe Team
Christina C. Lingham, Team Lead, PEGS Europe
13:45 Moderator’s Opening Remarks
Marie Kosco-Vilbois, Ph.D., CSO, NovImmune SA
13:50 Safety Considerations for Development of Immune Agonist and Immune Antagonist Biotherapeutics
Rakesh Dixit, Ph.D., DABT, Vice President, Research & Development, and Global Head, Biologics Safety Assessment,
MedImmune (A member of AstraZeneca Group)
In this keynote presentation, the challenges of biotherapeutics impacting on the immune response, and the challenges investigators face managing, dose, scheduling, and satisfying the regulatory requirements will be discussed. The checkpoint pathways modulation
used for cancer immunotherapy has a natural role in controlling autoimmune diseases such as Type 1 Diabetes and Lupus. Immunotherapies in general, and technologies modifying T cell function and those involving cytokines present dangers of cytokine
storm, autoimmune disease, cardiovascular disorders, and additional challenges, especially when used in combination. Strategies to manage and mitigate immune related safety events will be presented.
14:30 Learning What Works from Successful Tumour Infiltrating Lymphocyte Therapy
Andrew Sewell, Ph.D., Professor, Division of Infection and Immunity, Cardiff University School of Medicine
Over 20% of melanoma patients that have been refractory to other treatments undergo complete lasting remission after adoptive cell transfer of tumor-infiltrating lymphocytes (TILs). Dissection of these extraordinary successes by examining the dominant
tumor-reactive T-cell clonotypes in the TIL infusion product and patient blood after ‘cure’ has revealed some surprising, exciting new HLA-restricted and non-HLA restricted targets that are expressed by many other tumour types.
15:10 Widening the Therapeutic Index: The Next Generation of Antibody-Drug Conjugates (ADCs)
John M. Lambert, Ph.D., Executive Vice President Emeritus and Distinguished Research Fellow, ImmunoGen, Inc.
ADCs with potent tubulin-acting and DNA-acting agents can be effective anti-cancer agents with good TI. However, not all cell-surface targets have proven susceptible to the development of effective ADCs utilizing the first-generation ADC chemistries.
Each element in the ADC design, the antibody, the payload, and the linker (both site of attachment on antibody and payload-release mechanism) are important considerations. Application of the growing “ADC Toolbox” to current and future
ADC developments will be discussed.
15:50 Refreshment Break in the Exhibit Hall with Poster Viewing
16:50 Chairperson’s Remarks
Chris Lloyd, Senior Scientist, Protein Engineering, Antibody Discovery and Protein Engineering (ADPE), MedImmune
16:55 Identification of Biomarkers by ORFeome Phage Display
Michael Hust, Ph.D., Group Leader, Institute for Biochemistry, Biotechnology and Bioinformatics, Biotechnology,
Technical University of Braunschweig
The identification of biomarkers from pathogens is a prerequisite for the development of vaccines and diagnostic assays. We are using phage display to identify immunogenic proteins using bacterial genome libraries. In this presentation, the technology
will be described and the results of our project on the identification of biomarkers related to Inflammatory Bowel Disease (IBD) from microbiota derived metagenomic libraries will be presented.
17:25 Multivalent pIX Phage Display Selects for Distinct and Improved Antibody Properties
Geir Åge Løset, Ph.D., Researcher, Centre for Immune Regulation and Department of Biosciences, University
of Oslo
Phage display allows for identification of a multitude of specificities, but to identify optimal lead candidates remains a challenge. The pIX capsid is natively expressed and assembled into the phage particle independently of a signal sequence. This
feature translates to pIX fusions and we show that antibody display using multivalent pIX display results in substantially improved retrieval of desired specificities with favorable biophysical properties in de
novo selection.
17:55 Design, Build and Validation of Isogenica’s Fully Synthetic Human Fab Library
Guy Hermans, Ph.D., CSO, Isogenica Limited
We will present validation data on our recently developed fully synthetic human Fab library. The diverse set of heavy and light chain germlines, combined with the fully synthetic nature of the randomized CDR1, -2 and -3 regions ensures many issues
with immune and naïve libraries can be overcome. Use of Colibra™ DNA library build technology allowed for the removal of CMC liability motifs from both the framework as well as CDR regions.
18:25 Welcome Reception in the Exhibit Hall with Poster Viewing
19:25 End of Day
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TUESDAY 14 NOVEMBER
07:45 Registration and Morning Coffee
08:30 Chairperson’s Remarks
Ana Barbas, Ph.D., Coordinator, Bayer Satellite Laboratory at iBET, iBET and Bayer Portugal SA
08:35 The Good, the Bad and the Ugly Antigen: Deep Sequencing Analysis of Selection Outputs Is Revealing Antigen-Specific Enrichment Patterns
Stefan Ewert, Ph.D., Senior Investigator I, NIBR Biologics Center, Novartis Pharma AG, Switzerland
We developed a test system to classify antigens falling into three categories of suitability in provoking antibodies and applied deep sequencing to understand underlying sequence motifs of antibodies for each category of antigen. “Good”
antigens are able to provoke a robust enrichment of specific sequences while “bad” antigens are showing no change compared to the initial library diversity and “ugly” antigens are showing non-specific enrichment.
09:05 Generation of a Dual Protease Inhibitor Antibody
Andrew E. Nixon, Ph.D., Vice President, Biotherapeutics Molecule Discovery, Boehringer-Ingelheim
Bispecific antibodies have become an important class of antibody drugs with application in a variety of therapeutic areas. Here we will discuss identification of a pair of serine protease inhibitors from a phage display library,
in vitro and in vivo characterization and creation of a dual inhibitory bispecific antibody. Finally, we will review alternate bispecific antibody formats, challenges and
applications.
09:35 Problem-Solving Breakout Discussions (View All Breakout Discussions)
How to identify new biomarkers using phage display
Moderator: Michael Hust, Ph.D., Group Leader, Institute for Biochemistry, Biotechnology and Bioinformatics, Biotechnology, Technical University of Braunschweig
- Examples for biomarker/immunogenic proteins discovery using phage display
- How to construct these libraries and perform the selection
- Advantages/disadvantages of the phage display based approach compared to other technologies (2D-PAGE, Protein/Peptide Arrays....)
Involvement of Neoepitops in Disease Pathogenesis
Moderator: Ahuva Nissim, Ph.D., Reader, Molecular Targeting, Biochemical Pharmacology, William Harvey Research Institute, Queen Mary University of London
- Formation of neoantigens in disease: (a) Post translational modification of antigens (chemical and enzymatic), (b) Hybrid proteins/peptides
- Neoantigens and autoimmune disease
- Neoantigens and cancer
10:35 Coffee Break in the Exhibit Hall with Poster Viewing
11:15 KEYNOTE PRESENTATION: Innovative Strategies for Antibody Lead Discovery and Optimization at Bayer
Rene Hoet, Ph.D., Head, Antibody Lead Discovery, Bayer AG
This talk will describe HT Functional IgG screening from Fab phage display libraries, as well as phenotypic antibody screening used to expand the functional-epitope target space for biologics. Successful examples of antibody phage selections and
target identification for cancer cell internalizing antibodies that could be developed into antibody drug conjugates will be outlined.
11:45 Phage Display and Generation of Bispecific Antibodies
Katarina Radošević, Ph.D., Global Head Biologics Research, Sanofi R&D, Paris,
France
Novel antibody formats that target multiple antigens are steadily gaining interest in the development of new biologics. Appropriate biophysical characteristics and diversity of antibodies are some of the essential steps for obtaining highly efficacious
and developable molecules. Library approaches, such as phage display, can significantly contribute to the design of multi-specific antibodies. The approaches Sanofi is taking in this area will be addressed during this talk.
12:15 No Wash Multiplexed Immunoassays: sol-R Beads and Mirrorball – Simplifying the ELISA Workflow
Paul Wylie, Ph.D., Head of Applications, TTP Labtech
We have developed a range of validated bead based immunoassays that can be easily automated in a simple workflow. Combining sol-R beads and the mirrorball, no wash cell or bead-based assays provide process efficiencies over standard Flow or ELISA
assay platforms, enabling you to do more with less.
12:30 TrueRepertoire™: High-throughput Antibody Discovery Platform by High-Fidelity NGS and Clone Retrieval
Hyoki Kim, President and CEO, Celemics, Inc.
NGS-based antibody library analysis faces key issues of sequencing error, short read length and need of gene synthesis for binding assay. Here, we will discuss our developed platform, TrueRepertoireTM that enables to obtain accurate read of
antibody libraries and provides the corresponding scFv gene for further characterization.
12:45 Luncheon Presentation: Functional Reconstruction of Active Protein Surfaces using CLIPS-Constrained Peptides
Peter Timmerman, CSO, Pepscan Therapeutics B.V.
The lecture focusses on recent epitope mapping studies of structurally complex antibody binding sites. The studies highlight the importance and use of CLIPS-technology, a proprietary technology for manufacturing and HTS-screening of conformationally-constrained
peptides as protein mimics in general. Also illustrated is the development of (CLIPS-)constrained protein-mimics as peptide-vaccins (e.g. VEGFtrunc), or for antibody generation toward structurally complex proteins, like GPCR’s.”
13:15 Session Break
13:30 Dessert Break in the Exhibit Hall with Poster Viewing
14:00 Chairperson’s Remarks
Ahuva Nissim, Ph.D., Reader, Molecular Targeting, Biochemical Pharmacology, William Harvey Research Institute, Queen Mary University of London
14:05 Insights into the Pathogenesis of Multiple Sclerosis from Biological Therapies
Monica Calado Marta, M.D., Ph.D., Neuroimmunology Unit, Neurosciences & Trauma, Blizard Institute QMUL, Barts & The London School of Medicine and Dentistry
Current MS treatments are believed to act via T cell inhibition. However, most therapies have been shown to deplete CD19+, CD27+ memory B cells, in particular, anti-CD52 and anti-CD20-depletion therapies. In comparison, memory B cells
are augmented by B cell activating factor (atacicept) and tumor necrosis factor (infliximab) blockade that worsen MS. The memory B cell hypothesis is consistent with therapeutic, histopathological and aetiological aspects of MS.
14:35 The Role of Molecular Imaging in the Development of Targeted Biopharmaceuticals
Jane Sosabowski, Ph.D., Senior Lecturer, Preclinical Molecular Imaging, Centre for
Molecular Oncology, Barts Cancer Institute, Queen Mary University of London
Molecular imaging has become an essential part of the drug development process. Most targeting biomolecules can be radiolabeled with metals or halogens in order to visualize and quantify their behavior in vivo.
This talk will concentrate on the use of whole body PET/CT and SPECT/CT imaging in evaluating single variable domain antibodies selected by phage display to target specific tissues.
14:55 Triple Vector for Discovery of Antibody Molecules in Full Therapeutic Format
Maria Pajuelo, Ph.D., CSO, Fairjourney Biologics
A new vector not only for phage display and production of soluble antibody fragments fused to human Fc in bacteria, but also for production in mammalian cells will be described. Ultimately the selection of immunological effector function
bearing bivalent molecules, bypassing the cloning into mammalian expression vectors, will accelerate the drug discovery process. The selection of anti-human CXCR4 VHH-human Fc molecules from naïve repertoires using this vector
will be presented.
15:15 Discovery and Development of Topically Applied Biologics for the Treatment of Mild-to-Moderate Psoriasis Based on a Transgenic Platform Producing 100% Human VHs, Rescued and Selected by Phage Display
Peter Pack, Ph.D., CEO, Crescendo Biologics Ltd.
Crescendo has developed the clinical Humabody® candidate CB001 of high stability and robustness, targeting IL17 for the topical treatment of mild-moderate psoriasis. In a range of preclinical models, the anti-IL17 Humabody®
effectively penetrates tissues and diseased skin in contrast to conventional IgGs. Positive, dose dependent readouts obtained using a range of cytokine/chemokine assays strongly indicate that psoriasis can be treated with very
low concentrations of topically applied Humabody® VH biologics.
15:35 Further Advancements for Human Antibody Discovery
Vera Molkenthin, Ph.D., Chief Scientist, AbCheck s.r.o.
AbCheck has developed Mass Humanization to generate humanized libraries. This approach utilizes batch cloning of CDR3 immune repertoires from immunized rabbits into selected human frameworks containing specifically diversified CDR1
and CDR2 regions. For selecting high affinity binders from the resulting, highly diverse library, AbCheck routinely applies Phage or Yeast Display under various conditions. In this talk, AbCheck will present new technological developments
regarding its human antibody discovery and optimization platform.
16:05 Refreshment Break in the Exhibit Hall with Poster Viewing
Chairperson’s Remarks
John McCafferty, Ph.D., Co-Founder, Director and CEO, IONTAS Ltd
16:45 Selection of Nanobodies That Block Gating of the P2X7 Ion Channel with High Specificity and Effectivity
Friedrich Koch-Nolte, M.D., Professor, Immunology and Molecular Biology,
Institute of Immunology, University Medical Center Hamburg
Ion channels are important therapeutic targets, yet there remains a need for drugs with better selectivity and fewer side effects. Nanobodies, single domain antibodies from llamas, offer a means of developing specific biologics to
ion channels. The ATP-gated P2X7 ion channel drives inflammation by promoting the release of interleukin-1β. Using nanobody phage display libraries from P2X7-immunized llamas, we selected nanobodies that effectively block
ATP-induced gating of mouse or human P2X7.
17:15 Selection Strategies to Identify Novel Bioactive Cyclotides from Phage Display Libraries
William Eldridge, Ph.D., CSO, Cyclogenix, Ltd.
This talk will review the work they are doing on “knottin” peptides displayed on phage and how they are doing selections on cells and selections for peptides that driver transport across the gut and the blood-brain barrier.
17:45 Generating Ion Channel Blocking Antibodies by Fusing Cysteine-Knot Miniproteins into Antibody CDR Loops
John McCafferty, Ph.D., Co-Founder, Director and CEO, IONTAS Ltd
Using phage display, we have demonstrated that a “model” knottin (trypsin-blocking EETI-II) can be inserted via short linker peptides into peripheral diversity loops (CDRs) of antibodies. Furthermore, we also demonstrate
that binding specificity of both antibody and peptide can be engineered. In addition, we demonstrate blocking of Kv1.3 and ASIC1a ion channels by substituting alternative cysteine-rich peptides. Thus the resulting “KnotBody”
retains the advantage of ion channel blocking activity from the peptide while enjoying the extended half-life and additional specificity conferred by the antibody molecule.
18:15 End of Display of Biologics
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