The 4th Annual Engineering Antibodies conference at PEGS Europe presents the latest antibodies to watch, and explores technologies and new approaches to discover, design and engineer novel modalities and new platforms for existing and challenging targets.
The conference will also explore new techniques such as deep sequencing, in silico engineering and gene editing to help further the understanding of the sequence and structure-function of the molecules, and close the gap from bench to clinic.
WEDNESDAY 20 NOVEMBER
07:45 Registration (Foyer A) and Morning Coffee (Foyer D)
08:30 Chairperson’s Opening Remarks
Janice M. Reichert, PhD, Executive Director, The Antibody Society, and Editor-in-Chief, mAbs
08:35 TriTAC: A Tri-Specific T Cell Engaging Platform for the Treatment of Solid Tumors
Bryan D. Lemon, PhD, Senior Director, Protein Science, Harpoon Therapeutics, Inc.
T cell engagers are protein therapeutics that tether T cells to surface antigens on tumor cells, leading to activation of those T cells and destruction of the tumor. The TriTAC (tri-specific T cell activating construct) technology is designed to optimize
the therapeutic window by addressing half-life and stability limitations of pioneering T cell engagers (e.g., bispecific T bell engagers, or BiTEs). HPN424 first entered the clinic in 2018 and is under development for the treatment of metastatic
castration-resistant prostate cancer.
09:05 The Making of a Biparatopic Molecule
Garces, PhD, Senior Scientist, Biologics Optimization, Amgen
Multispecifc molecules show great promise as a vehicle to boost pharmacokinetic properties such as therapeutic efficacy and controlled toxicity. Biparatopic antibodies, bispecific molecules that recognize two unique and non-overlapping epitopes on
the same antigen/target, have been shown to facilitate receptor internalization, promote superior antagonistic effect, among others. Here, we describe the making of a biparatopic molecule that recognizes two distinct domains on our target receptor.
Using a structural-guided approach we have designed, generated and demonstrated that these novel bispecific formats can efficiently bind to both epitopes on the same molecule whereas cross-binding is restricted by the insertion of selected linkers.
09:35 RNAntibody® – A Potent mRNA Technology for Antibody Therapies
PhD, Senior Scientist, CureVac
The delivery of genetic information has emerged as a promising alternative to overcome drawbacks associated with the use of recombinant proteins in protein therapies. Recently, we demonstrated that a single injection of antibody-encoding mRNA
rapidly leads to high neutralizing antibody titers in animals, sufficient to provide fast protection against lethal rabies infection or botulinum intoxication. Additionally, we demonstrated that our RNAntibody technology is able to generate
therapeutically effective amounts of antibodies in two different mouse models for malignant diseases.
10:05 An Integrated Approach to Managing Immunogenicity Risk and Optimum Protein Design
Jeremy Fry, PhD, Director of Sales, ProImmune, Ltd.
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
10:35 Coffee Break in the Exhibit Hall with Poster Viewing (Rio Pavilion)
11:15 Targeted Thorium Conjugates (TTCs): A New Modality for the Treatment of Cancer Utilizing Alpha Particle-Based Radiotherapy
Cuthbertson, PhD, Head of Thorium R&D, TCR, Bayer AS
This talk will cover many preclinical aspects of cancer therapy using tumor antigen specific antibodies for the delivery of alpha particle radiation to tumors. The core elements of targeted alpha therapy will be explained along with a selection
of data from in vitro and in vivo models demonstrating the potential of this versatile platform.
11:45 The Contorsbody, a Format for Agonism: Design, Structure, Function
Guy Georges, PhD,
Expert Scientist, Large Molecule Research, Roche Innovation Center Munich
The contorsbody is a novel Ab format designed to achieve receptor dimerization. A hybrid structure combining X-ray diffraction and cryo electron microscopy data reveals a special architecture for this format. Depending on receptor and epitope,
regular IgG antagonist antibody (ligand blocker or dimerization blocker) can be switched into full agonist when transformed into mono-specific bivalent contorsbody. Bispecific contorsbodies can be obtained via the “Knob into Hole”
technology so that receptor hetero-dimerization or hetero-clustering can be achieved.
12:15 Preclinical Development of ELN/22, a Novel “Super-Neutralising” Solomer™ Specific for Human TNF-Alpha
Obinna Ubah, PhD,
Senior Research Scientist, Biologics Drug Discovery and Protein Engineering, Elasmogen Limited, Aberdeen
TNFα is implicated in a host of chronic autoimmune inflammatory diseases. Therapeutic targeting and subsequent neutralisation of TNFα has demonstrated positive clinical outcomes, however a significant percentage of these patients fail
to respond or have their disease satisfactorily controlled with many patients discontinuing treatment due to life-threatening side effects. The ELN/22 drug candidate is an empirically designed novel biologic with a unique mechanism of TNFα
neutralisation and delivers a superior efficacy in an in vivo model of polyarthritis. In addition, the ELN/22 has been designed to reduce the risk of ADA and serious side effects development.
12:45 Industrializing IO Therapeutic Discovery Platforms: Multispecifics, Engineered TCRs and CARs
Jana Hersch, PhD, Scientific Consultant, Biologics, Genedata
Novel classes of bio-molecules are currently evaluated for their use in cancer immunotherapy. Bi- and multi-specific antibodies, Ab-cytokine fusion proteins, non-Ig scaffolds, chimeric antigen receptors (CARs), engineered TCRs and TCR-based bispecific
constructs promise significant advantages. However, these highly engineered molecules pose new challenges in design, engineering, cloning, expression, purification, and analytics. We present an infrastructure that addresses these challenges
and enables the industrialization of these various novel therapeutic platforms.
13:15 Luncheon Presentation I: Integrated mAb Pipeline from Virtual Machine Learning to Transposon Mediated Cell Line Development
Claes Gustafsson, Co-Founder and CEO, ATUM (formerly DNA2.0)
Monoclonal antibodies in their many divergent formats have revolutionized medicine and today represents >$100B/year in pharmaceutical sales. ATUM has built an integrated pipeline from generation of antigens via affinity maturation, developability,
engineering and humanization all the way through scale up and stable cell line generation. The presentation will include case studies highlighting the process, each step uses technological breakthroughs in synthetic biology, machine learning,
LIMS data integration, robotics and engineered transposases to ensure maximum efficiency.
13:45 Luncheon Presentation II: Quality. Speed. Value. Therapeutic Antibody Discovery in Challenging Projects Using AlivaMab Mouse and AlivaMab Discovery Services
Larry L. Green, PhD, CEO, Ablexis and AlivaMab Discovery Services
AlivaMab Mouse delivers superior molecular diversity and greater numbers of high-affinity, high-potency therapeutic antibody candidates with faster timelines than other platforms. AlivaMab Discovery Services uses its proprietary processes to overcome
the challenges of modern antibody drug discovery with industry-leading timelines. Case studies in the rapid generation of therapeutic quality antibodies with challenging discovery plans including against several GPCRs will be presented.
14:15 Session Break
14:30 Chairperson’s Remarks
Fernando Garces, PhD, Senior Scientist, Biologics Optimization, Amgen
14:35 FEATURED PRESENTATION: Antibodies to Watch in 2020
M. Reichert, PhD, Executive Director, The Antibody Society, and Editor-in-Chief, mAbs
The “Antibodies to Watch” talks and papers focus on antibody therapeutics in late-stage clinical studies, as well as those in regulatory review and recently approved in the United States and European Union. In this presentation,
Dr. Reichert will provide an overview of approvals granted to antibody therapeutics in these regions in 2019, and predict which antibody therapeutics may be approved or move to regulatory review in 2020.
15:05 KEYNOTE PRESENTATION: Explorations in Antibody Product Discovery
Janine Schuurman, PhD, Corporate Vice President Research & Innovation, Antibody Research & Technology, Genmab
The basis for successful product discovery is a conceptual product idea which integrates scientific information on the biology of the disease and the target (or targets), and a thorough understanding of antibody format opportunities. Nevertheless,
empirical screening of different target and antibody format combinations is critical, and often adaptations to initial assumptions are required before a novel product fulfilling the anticipated product criteria is discovered: the antibody
fine specificity, combined with the format chosen, can have a huge and not always predictable impact on the functional characteristics of novel antibody product. Examples will be shared and discussed.
15:35 Refreshment Break in the Exhibit Hall with Poster Viewing (Rio Pavilion)
16:15 Pipeline Update on GPCR and Ion Channel Antibodies
Catherine Hutchings, PhD, Independent Consultant
G protein-coupled receptors (GPCRs) and ion channels represent some of the most important drug target classes across a wide range of therapeutic areas. An update on antibody-based therapeutics in the pipeline will be provided outlining
the breadth and diversity of the target landscape, as well as progress in clinical development. This presentation will also include a summary overview of antigen formats that have been successfully combined with different platforms
to address the challenges inherently encountered with complex membrane protein targets.
16:45 Strategies to Isolate and Engineer Functional Antibodies against GPCR and Ion Channel Targets
Trevor Wilkinson, PhD, Associate Director, Antibody Discovery and Protein Engineering, AstraZeneca
G-protein-coupled receptors (GPCR) and Ion Channels represent challenging target classes for the isolation and optimization of therapeutic antibodies. In this presentation we review the technical challenges inherent in generating target
antigens suitable for antibody isolation and strategies to overcome these challenges. Progress in this area will be illustrated by case studies demonstrating how we have applied phage display and immunization strategies to isolate
and optimize functional, antagonistic monoclonal antibodies targeting GPCRs and ion channels.
17:15 ibody AD-214: A Novel Therapy for Fibrosis
Foley, PhD, CSO, AdAlta Pty Ltd.
AD-214 is a single domain i-body with affinity for CXCR4, a GPCR which is known to be upregulated in a number of cancers and recently has been implicated in fibrosis. We have shown that AD-214 can block the recruitment of fibrocytes into
the lungs of mice with bleomycin induced pulmonary fibrosis and that the anti CXCR4 i-bodies have anti-inflammatory and anti-fibrotic effects in several different animal models of fibrosis.
17:45 Networking Reception in the Exhibit Hall with Poster Viewing (Rio Pavilion)
18:45 Problem-Solving Breakout Discussions
TABLE 12: Challenges in Developing Antibodies against GPCRs and Ion Channels
Catherine Hutchings, PhD, Consultant
Trevor Wilkinson, PhD, Assoc Director, Antibody Discovery & Protein Engineering, AstraZeneca Biopharmaceuticals Unit
- What has been an enablement for use as an antigen format?
- What screening processes and assays have increased success?
- Are there emerging trends for how to address specific target classes?
- What else should we be integrating into the discovery flow?
TABLE 13: New Explorations in Antibody Engineering and Design
Moderator: Guy Georges, PhD, Expert Scientist, Large Molecule Research, Roche Innovation Center Munich
- Engineer the perfect antibody suited for becoming a therapeutic?
- Discover the ideal format?
- Design the adequate bi- multi- specific antibody?
19:45 End of Day
THURSDAY 21 NOVEMBER
08:00 Registration (Foyer A) and Morning Coffee (Foyer D)
08:30 Chairperson’s Remarks
Jonny Finlay, PhD, CEO, UltraHuman
08:35 Deep Sequencing of Natural Antibody Repertoires for Antibody Discovery and Optimization and Elucidation of Repertoire Properties
Isidro Hotzel, PhD, Senior Scientist, Antibody Engineering, Genentech
Hybridoma and B cell cloning remain the main technologies for antibody discovery based on mining of natural immune repertoires. Deep sequencing technologies are now used to enhance repertoire sampling of these technologies for rapid identification
of optimized antibody leads and de novo discovery. The application of deep sequencing to repertoire mining coupled to high throughput characterization of antibody panels also provides a broader view
of how natural immune repertoires are structured.
09:05 Commonality Despite Exceptional Diversity in the Baseline Human Antibody Repertoire
Briney, PhD, Assistant Professor, Immunology & Microbiology, Scripps Research Institute
09:35 A Comprehensive Screening Platform to Identify the Next Generation Targeted Cancer Immunotherapy Targets
Stefanie Urlinger, PhD, Vice President, Antibody Development, iOmx Therapeutics AG
We have developed a systematic, high-throughput genetic screening approach that enables the identification and comprehensive validation of novel immune checkpoint targets in human cancer cells. Inhibition of these targets by a broad range
of methods, such as CRISPR/Cas9 mediated gene knockouts, tool compounds or monoclonal antibodies, results in immune activation and enhanced T cell-mediated tumor cell killing in diverse tumor models. To date, we have validated various
novel immune checkpoint targets that drive unique and previously undescribed immune evasion biologies – paving the way for innovative future cancer immunotherapies.
10:05 Making an Antibody-based Therapeutic in 60 days: High-Throughput Discovery Applied to a Rapid Pandemic Response Platform
Sherie Duncan, PhD, Manager Partners & Programs, AbCellera
AbCellera’s antibody discovery technology combines sequence and functional data from single B cell screening with repertoire sequencing of immune responses and intuitive analysis of the resulting large panels of antibodies and high-throughput
characterization data using AbCellera’s CeliumTM tool creates a powerful platform for therapeutic discovery. Under the DARPA Pandemic Prevention Platform (P3), AbCellera is applying this technology to the rapid development of
field-ready medical countermeasures within 60 days of isolating a viral pathogen.
10:35 Coffee Break in the Exhibit Hall with Poster Viewing (Rio Pavilion)
11:15 Antibody Polyspecificity as a Critical Development Risk in Therapeutic Antibody Development
Finlay, PhD, CEO, UltraHuman
UltraHuman Eight has shown for the first time that antibody polyspecificity can be a direct cause of unpredictable side effects in the clinic. Novel insights into identification of off-target binding events and their remediation to create
ideal, low-risk clinical leads will be presented.
11:45 Advancing Therapeutic Protein Development Using a Novel O-Glycan-Based Conjugation Approach
Monika Papworth, PhD, Senior Scientist, Antibody Discovery and Protein Engineering, AstraZeneca
Our technology represents an amalgamation of genome editing, cell line metabolic engineering and the application of a novel peptide-based tag to efficiently generate site-specific, homogeneously-labelled recombinant secretory proteins
containing modified O-glycans. We demonstrate the facile addition of genetically-encoded O-glycosylation motifs and the robust incorporation of functionalised O-glycans to recombinant proteins using a UDP-galactose-4-eperimase (GALE)
knockout, serum-free, cell expression system. This technology represents an elegant, controllable approach to generate bespoke, consistently labelled recombinant proteins ‘On Demand’.
12:15 Luncheon Presentation I: Computational Immuno-Engineering Therapeutics Against Hard Targets: Cracking into GPCR Antagonists & Blood-Brain Barrier
Sarah Ives, Principal Scientist & Director, Contract Research, Distributed Bio
Immune checkpoint inhibitors make attractive yet challenging targets for antibody discovery, where a therapeutic-ready monoclonal antibody can take years to be discovered and subsequently engineered. Here we describe a computational antibody
library design that was optimized for both sequence diversity and engineering fitness through the analysis of thousands of human antibody repertoires. The technology enables routine discovery against previously challenging targets
including GPCRs, pMHC complexes, and rare epitopes.
12:45 Luncheon Presentation II: Synthetic
Biology Capabilities of the BioXp™ 3200 System
Lindsey Wolf, Product Manager, Catalog Reagents, SGI DNA Inc.
The BioXp™ 3200 is a benchtop platform that enables researchers to rapidly synthesize high-quality DNA Libraries, Tiles and Clones in an automated fashion by simply uploading sequence files to a customer portal. The platform dramatically
improves workflow productivity for a variety of applications such as protein production, antibody library generation and cell engineering giving more control over genomic workflows. This talk will focus on some of our recent developments
for new capabilities on the BioXp.
13:15 Dessert Break in the Exhibit Hall with Poster Viewing (Rio Pavilion)
14:00 End of Engineering Antibodies
17:00 Dinner Short Course Registration*
17:30 – 20:30 Dinner Short Courses
Recommended Short Course*
SC6: Selection, Screening and Engineering for Affinity Reagents - LEARN MORE
*Separate registration required.