Today’s protein scientists need to be creative and think outside the box. As standard monoclonal antibodies give way to new and diverse therapeutic modalities, protein scientists have to develop strategies that can better engineer these complex
molecules, and improve their targeting, specificity, binding, intracellular penetration and bioactivity.
PEGS Europe’s 3rd Annual Engineering Antibodies invites scientists to present their creativity in designing novel antibody formats or alternative platforms, and in leveraging strategies and technologies to overcome challenging
intracellular and membrane targets.
Final Agenda
Day 1 | Day 2 | Download Brochure | Interactive Speaker Biographies
WEDNESDAY 14 NOVEMBER
07:45 Registration (Foyer C) and Morning Coffee (Foyer D)
08:30 Chairperson’s Remarks
Ulrich Brinkmann, PhD, Expert Scientist, Molecular Engineering, Roche
08:35 KEYNOTE PRESENTATION: Grp 94, an Intracellular Target of Antibody-Based Immunotherapy of Malignant Diseases – Opportunities and Challenges
Soldano Ferrone, MD, PhD, Professor, Surgery, Massachusetts General Hospital, Harvard Medical School
The scFv W9 has been isolated from a phage display human antibody library. This antibody has the unique specificity to recognize an extracellular epitope of the heat shock protein Grp94. The characteristics and functional properties of this antibody
will be described. In addition, the obstacles to the clinical applications of this and the strategies to overcome them will be discussed.
09:05 Engineering Alphabodies to Target Intractable Intracellular Cancer Targets
Yvonne McGrath, PhD, CSO, Complix
Alphabodies comprise a triple helical protein scaffold that can be engineered to bind target proteins with high specificity and affinity. Further modifications allow these biologics to traverse the cell membrane and inhibit disease-associated intracellular
targets. A panel of these Alphabodies has been engineered to bind and inhibit important oncology intracellular targets hitherto considered intractable with conventional small molecules. Functional assessment of a selection of these Alphabodies
will be presented.
09:35 Generating Potent and Selective Inhibitors of Kv1.3 Ion Channel by Fusing Venom Derived Mini Proteins into Peripheral CDR Loops of Antibodies
Aneesh Karatt-Vellatt, PhD, Group Leader, Antibody and Protein Engineering, IONTAS Ltd.
Pathogenic TEM cells drive many autoimmune disorders and are uniquely dependent on the Kv1.3 channel. A number of venom derived cysteine-rich mini-protein inhibitors of Kv1.3 are being developed as potential drug candidates, but can suffer from manufacturing
difficulties, short half-lives and a lack of specificity. Using proprietary KnotBody technology, IONTAS has developed a panel of potent and selective Kv1.3 inhibitors that can be further developed as long acting immunomodulators for the treatment
of autoimmune disorders.
10:05 CRISPR Meditated Targeted Genome Editing & Extending the Reach of Transient Expression using Scalable Electroporation Technology
Christopher Mann, PhD, Director, Field Applications Scientist Team, MaxCyte
The way that potential biotherapeutics such as antibodies are designed, engineered and manufactured continues to evolve at molecular, cellular and process levels. Here we present case studies to highlight how genome editing and novel therapeutic design
are being combined with process optimization and scalability to enabling production of novel therapeutic formats while maintaining pressure to reduce timelines and cost.
10:35 Coffee Break in the Exhibit Hall with Poster Viewing (Pavilion 1)
11:15 Targeting the Matrix Metalloproteinase (MMP)-14/MMP-2/Integrin αvβ3 Axis with Multispecific N-TIMP2-Based Antagonists for Cancer Therapy
Niv
Papo, PhD, Group Leader, Assistant Professor, Biotechnology Engineering, Ben-Gurion University
The MMP-14/MMP-2/integrin αvβ3 axis thus constitutes a putative target for therapeutic interventions, but inhibitors that target this axis remain to be developed. Based on screening of a N-TIMP2 mutant library, we generated efficient protein
monomers and heterodimer antagonists that contain monovalent and bivalent binding epitopes to MMP-14 and integrin αvβ3. These results enabled us to investigate the individual roles of the three signaling molecules in various malignant
processes.
11:45 Multiple Mechanism of Ligand Blocking by Antibodies
Fernando Garces, PhD, Senior Scientist, Therapeutic Discovery, Amgen
Antibodies can be generated and selected to block the binding of a protein receptor to its protein ligand. In such cases, the set of molecules generated usually show low sequence diversity and a common inhibition mechanism. Here we present a case
study, where we have structurally characterized multiple antibodies, with high sequence diversity that recognize a protein receptor and block protein/ligand binding via several inhibition mechanisms.
12:15 The Molecular Landscape of the Immune Response following Treatment with Biologics
Yariv Wine, PhD, Assistant Professor, School of Molecular Cell Biology and Biotechnology, Tel Aviv University
The mechanisms that lead to the generation of ADAs and their molecular composition are unknown. We developed a new immunoassay to determine ADA level and their neutralizing capacity. We found that therapeutic mAb infusion mounts a vaccine boost like
response reflected in a rapid rise of lymphocytes post-infusion. B Cells were isolated and their repertoire features were determined by NGS. Collectively we found: i) an increase in lambda/kappa antibody light chain ratio in the neutralizing ADA
compartment; ii) an increase in ADA clonal polarization post-infusion.
12:45 An Integrated Approach to Managing Immunogenicity Risk And Optimum Protein Design
Jeremy Fry, DPhil, Director, Sales, ProImmune
Integrated platforms can be used to mitigate immunogenicity risk and characterize immune responses during the drug design and development stages. ProImmune offers mutational activity mapping for optimal protein design, DC-T/T cell proliferation assays
for biologic lead selection/optimization, a Mass Spectrometry assay for characterization of antigen presentation; HLA-peptide binding assays to characterize individual epitopes & undiluted whole blood cytokine storm assays.
13:15 Luncheon Presentation I: Build Better Biologics with Machine Learning and Synbio
Claes Gustafsson, Co-Founder and CCO, ATUM (formerly DNA2.0)
This presentation will showcase how ATUM combines recent developments in genome engineering, automation, big data and product analytics to increase efficiency of engineering and developability of biologics and cell lines. Cell lines generated using
the LeapIn® transposase combined with optimized vector constructs, proprietary codon optimization and QSAR-based protein engineering allow for an information rich and efficient optimization of mAbs, bispecifics, CAR-T molecules, and the increasingly
complex biologics approaching the market place.
13:45 Luncheon Presentation II: Overcoming Tolerance by
Deep Mining of Natural Immune Repertoires
Veronique Lecault, PhD, Co-Founder, AbCellera
Antibodies from natural immune responses are widely regarded as superior to those generated by display technologies; however, immune tolerance poses a serious challenge for targets with high inter-species homology. Insoluble and poorly immunogenic
targets such as membrane proteins exacerbate this challenge. We show how AbCellera’s ultra-deep screening technology overcomes these challenges, producing hundreds of diverse rodent antibodies against targets with 100% rodent-human
homology, including G protein-coupled receptors.
14:15 Session Break
14:30 Chairperson’s Remarks
Philip M. Kim, PhD, Associate Professor, Donnelly Centre, University of Toronto
14:35 Use of Small and Stable Antibody Scaffold Fv-clasp to Facilitate Structural Studies of Drug-Target Molecules
Junichi Takagi, PhD, Professor, Laboratory, Protein Synthesis and Expression, Institute for Protein Research, Osaka University
“Fv-clasp’’ is an artificially designed, small (˜37 kDa) two-chain antibody fragment format compatible with bacterial expression and is applicable to any IgG antibodies. The conformational rigidity and high heat stability of
Fv-clasp contributed to its superior “chaperoning” activity over conventional Fab fragment, and facilitated the structure determination of many drug target proteins with high conformational flexibility.
15:05 Multi-Specific, Multi-Valent and Bi-Paratopic Nanobodies: Progress toward the Clinic
Carlo Boutton, PhD, Director, Technology & Information Management, Ablynx NV
Small Nanobodies with their modular design are a perfect starting point for generating multivalent and multispecific therapeutics in a wide range of human diseases. The formatting flexibility of the platform allows the development of the most optimal
drug formats. The development of Nanobodies® and their progress towards the clinic will be shown by a number of examples.
15:35 Refreshment Break in the Exhibit Hall with Poster Viewing (Pavilion 1)
16:15 V565 Is an Orally-Administered, Protease-Resistant, Anti-TNF Domain Antibody for the Treatment of Inflammatory Bowel Disease
Kevin Roberts, PhD, Senior Scientist, VHsquared Ltd.
V565 is an anti-TNF domain antibody for oral administration in IBD patients, engineered to resist intestinal proteases. Oral dosing of V565, formulated in enteric-coated minitablets, resulted in micromolar levels of active V565 in the ileal fluid
of volunteers fitted with ileostomy bags and in the faeces of Crohn’s disease patients. Oral administration to five ulcerative colitis patients for 6 to 7 days resulted in V565 localisation to the lamina propria and inhibition of mucosal
inflammatory processes.
16:45 Development of mRNA-Encoded Bispecific Antibodies Targeting Solid Tumors
Hayat Bähr-Mahmud, PhD, Deputy Head, Bispecific
Antibodies, BioNTech
Successful application of many T cell-engaging bispecific antibodies is hindered by manufacturing challenges and short serum half-life. We circumvented these limitations by treating mice with in vitro-transcribed
(IVT) pharmacologically optimized and nucleoside-modified mRNA encoding the antibody. We achieved sustained endogenous synthesis of the antibody, which eliminated advanced tumors as effectively as the corresponding purified bispecific antibody.
Due to the fast manufacturing process of pharmaceutical mRNA, the RiboMAB approach could accelerate the clinical development of novel bispecific antibodies.
17:15 Development of Highly Potent T Cell Receptor Bispecifics Targeting Tumor-Specific HLA Ligands
Sebastian Bunk, PhD, Director, Immunology, Immatics Biotechnologies GmbH
T cell receptor (TCR)-based immunotherapy has emerged as a promising treatment modality for malignant diseases. Immatic’s bispecific TCR molecules utilize affinity maturated and selective TCRs for targeting of tumor-specific, human leucocyte
antigen (HLA)-bound peptides as identified by the target discovery engine XPRESIDENT®. The TCRs are engineered into our highly active bispecific TCR scaffold comprising a T cell-engaging antibody for potent redirection and activation of T
cells and resulting in stable molecules with extended serum half-life.
17:45 Networking Reception in the Exhibit Hall with Poster Viewing (Pavilion 1)
18:45 Problem-Solving Breakout Discussions (Foyer E&F)
Computational Protein Strategies
Moderators: Philip M. Kim, PhD, Associate Professor, Donnelly Centre, University of Toronto and Samuel Coulbourn Flores, Docent, Dean, Swedish National Graduate School in Medical Bioinformatics, Biochemistry and Biophysics, Stockholm University
- Roles for machine learning/AI
- Free energy methods vs. rosetta or other forcefields
- Future of computational design vs. screening methods
Optimization Strategies for Generation of Engineered Antibodies
Moderator: Christopher Mann, Director, Field Applications Scientist, MaxCyte
- Benefits and pitfalls of targeted genome-editing
- Current challenges to transient protein production
- Transient versus stable expression
- What are the main bottlenecks?
- Emerging technologies?
19:45 End of Day
Day 1 | Day 2 | Download Brochure
THURSDAY 15 NOVEMBER
08:00 Registration (Foyer C) and Morning Coffee (Foyer D)
08:30 Chairperson’s Remarks
Niv Papo, PhD, Group Leader, Assistant Professor, Biotechnology Engineering, Ben-
Gurion University
08:35 From Antibody-Targeted Toxins to Gene Editing: Disruption of Diphthamide Synthesis Genes and Resulting Toxin Resistance as a Robust Technology for Quantifying and Optimizing CRISPR/Cas9 Approaches
Ulrich Brinkmann, PhD, Expert Scientist, Molecular Engineering, Roche
Activity of antibody fusions harboring Pseudomomas Exotoxin derivatives requires diphthamide on eEF2. Diphthamide therefore serves as biomarker for immunotoxin efficacy; cells without diphthamide are toxin resistant. This phenotype can also be
applied to identify and quantify events that result from CRISPR/Cas9 editing. DPH gene editing followed by toxin selection provides a simple robust method to differentiate and quantify homozygous/ heterozygous inactivation and integration
events, and to optimize specificity and efficacy of editing procedures.
09:05 High-Throughput Antibody Engineering in Mammalian Cells by CRISPR/Cas9-Mediated Homology-Directed Mutagenesis
Sai Reddy, PhD, Assistant Professor, Biosystems Science and Engineering, ETH Zurich
Homology-directed mutagenesis (HDM) extends the concept of CRISPR/Cas9-mediated homology-directed repair to generate site-directed mutagenesis libraries in mammalian cells. Following cleavage by the Cas9 protein, single-stranded oligonucleotides
containing degenerate codons serve as the repair template, providing integration of sequence diversity into the genome. We used HDM to generate libraries in the antibody CDRH3, and combined this with a mammalian surface display platform for
high-throughput screening.
09:35 A Case Study in Adaptability: Exemplification of the Power of UCB’s Core Discovery Platform through the Discovery of a Potent Anti-Tau Antibody
Dale Starkie, MSc, Senior Scientist, UCB Celltech
Here we describe the use of a number of cutting-edge antibody discovery technologies to efficiently interrogate the B cell repertoire of immunised animals and humans to identify rare antibodies with desirable characteristics. We employ a high-throughput
automated B cell culture screening platform to mine out the memory B cell repertoire and a novel fluorescence-based proximity secretion assay to sample the plasma cell repertoire. We will discuss the use of multiple immunisation strategies
utilising several forms of antigen and the discovery of an anti-tau lead antibody candidate capable of blocking uptake and aggregation of tau from three distinct human tauopathies in a novel robust and quantitative Tau seed uptake cellular
assay.
10:05 Antibody Protein Sequencing with Mass Spectrometry
Mingjie Xie, CEO, Rapid Novor Inc.
Many applications in antibody engineering require the direct sequencing of antibody proteins. At Rapid Novor (rapidnovor.com), we have developed a robust workflow and routinely sequenced antibody proteins. Here we share the success experiences,
examine common mistakes novices make, and present our practices to ensure the correctness of every amino acid.
10:20 NEW: The SCORE Technology, a Novel Label-Free HTS Tool for Drug Discovery
Julia Schuette, PhD, Head, Marketing & Sales, Biametrics GmbH
In high-throughput screening, the more you can screen, with the most sensitive technology, the higher likelihood of finding the best candidates. SCORE technology combines a microarray approach with kinetics to offer richer data sets that improve
target identification. This results in better lead candidates, accelerating your drug discovery pipeline.
10:35 Coffee Break in the Exhibit Hall with Poster Viewing (Pavilion 1)
11:15 Integrated Computational Design and Experimental Selection Leads to Custom Targeted Biologics
Philip M. Kim, PhD, Associate Professor, Donnelly Centre, University of Toronto
I will present our technology platform on integrating a number of different computational protein strategies (including classic protein design, thermodynamic integration and machine learning) with high-throughput selection strategies (including
phage display, yeast-2-hybrid and phenotypic selections in mammalian cell culture) to obtain custom targeted biologics.
11:45 Collecting Structural Data to Improve Predictions of Protein-Protein Interface Mutagenesis
Samuel Coulbourn Flores, Docent, Dean, Swedish National Graduate School in Medical Bioinformatics, Biochemistry and Biophysics, Stockholm University
Predicting the effect of mutations on protein-protein binding affinity is important for biotechnology and could open the door to in silico affinity maturation. Perturbative, empirically trained potentials such as FoldX are currently superior to physics-based and bioinformatical methods, but improvements in precision have slowed. In the meantime, structural data has continued to accrue, leading to growing redundancy in the Protein Data Bank. I will show how homologyScanner (server: http://biodesign.scilifelab.se/) harnesses redundant structures to diversify the conformational input to perturbative potentials, leading to substantial increases in precision.
12:15 Luncheon Presentation I: Naturally Optimized Human Antibodies from the OmniChicken™ Platform
Phil Leighton, PhD, Director, Molecular Biology, Ligand Pharmaceuticals
Because of their phylogenetic distance from humans, chickens recognize a wider range of epitopes on human targets than mammalian hosts, can deliver cross-reactive antibodies for pre-clinical studies that obviate the need for surrogate antibodies,
and recognize highly conserved human proteins that may not be immunogenic in mammals. The OmniChicken™ has been engineered to express an immune response consisting of human antibodies and represents a next-generation
technology for the discovery of monoclonal antibody therapeutic candidates.
12:45 Luncheon Presentation II: The Systems Immunology Revolution: How Computational Design has Enabled Thousands of Clinic-Ready Antibodies in Weeks
Jacob G. Glanville, PhD, Founding Partner & CSO, Distributed Bio Inc.
13:15 Dessert Break in the Exhibit Hall with Poster Viewing (Pavilion 1)
14:00 End of Engineering Antibodies
17:00 Dinner Short Course Registration* (Foyer C)
17:30 – 20:30 Dinner Short Courses
Day 1 | Day 2 | Download Brochure