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Molecular evolution using the tools of phage, yeast, mammalian, antibody, and other display methods have yielded a staggering array of monoclonal and multi-specific antibodies, antibody-drug conjugates, immunotherapies, and numerous other constructs. The emergence of computational tools will be applied to improve selection, design, and efficacy of candidates. Conditional activation approaches will allow drug molecules to hit the tumour before they become activated, reducing off-target toxicity, and adverse events. Strategies to develop synthetic libraries and in vivo selection will be explored, along with the use of phage display to alter the functional activity of antibodies.

Sunday, 13 November

Registration Open12:00

Recommended Short Course*14:00

SC5: Machine Learning Tools for Protein Engineering  
*Separate registration required. See short courses page for details.

Monday, 14 November

Registration and Morning Coffee (Garden Room)07:30




Chairperson's Remarks

Ahuva Nissim, PhD, Professor, Antibody and Therapeutic Engineering, William Harvey Research Institute, Queen Mary University of London


Phage and Mammalian Display for Improved Therapeutic Antibodies

Pierre Martineau, PhD, Deputy Director, Functional Screening & Targeting of Cancer, IRCM Institut de Recherche en Cancerologie De Montpellier

Most display methods are based on antibody fragments binding activity. However, the preferred format for therapeutic applications is the IgG whose binding properties are affected by reformatting. We thus developed a display vector and an engineered mammalian cell line that allow both phage display and direct generation of cells stably secreting a monoclonal human IgG for functional screening. This system allows the screening of phage-derived antibody fragments as full-length IgG. In addition, using optimized selection procedures and synthetic library design, we show it is possible to directly select antibodies modulated by the pH for improved therapeutic targeting.


An Antibody Identified by Phage Display Targets a Protein Expressed in Both Cancer and Fibrosis

Aaron M. LeBeau, PhD, Associate Professor, Pathology & Lab Medicine, University of Wisconsin Madison

We developed a high-diversity single-chain variable fragment phage display library from naïve mice that allowed us to identify a suite of fragments that bound the serine protease Fibroblast Activation Protein (FAP). Expressed on the surface of both cancer-associated fibroblasts and myofibroblasts involved in wound healing, FAP is a target for cancer and fibrosis. Using a humanized version of our lead fragment in an IgG format, we were able to imaging FAP expression by positron emission tomography in murine models of prostate cancer and idiopathic pulmonary fibrosis with high accuracy and precision.   


Development of Potent Antagonist Against Target-of-Interest with Phage-Displayed Alternative Scaffolds

Yingnan Zhang, PhD, Senior Scientific Manager, Early Discovery Biochemistry, Genentech, Inc

A robust, alternative peptide-scaffolds platform, which consists of disulfide bond-constrained peptides that are resistant to thermal, proteolytic, and chemical degradation, has been developed with phage display. Ensembles of tens of libraries with overall diversity of 10^11 have been constructed. Binders against a target of interest have been identified from the libraries and further optimized with display technology and chemical synthesis to highly potent and stable leads with ideal pharmacological properties.

10:00 Extending the Specifica Generation 3 platform to affinity maturation and VHH libraries

Sarah D'Angelo, PhD, Chief Technical Officer, Specifica

The Specifica Generation-3 Library Platform is based on highly developable clinical scaffolds, into which natural CDRs purged of sequence liabilities are embedded. The platform directly yields highly diverse, high affinity, developable, drug-like antibodies, as potent as those from immune sources, with minimal need for downstream optimization. This talk will discuss extension of the Platform to VHH libraries and lead antibody improvement, with simultaneous enhancement of both affinity and developability.

Coffee Break in the Exhibit Hall with Poster Viewing (Verdi and Vivaldi 1&2)10:30



Chairperson's Remarks

E. Sally Ward, PhD, Director, Translational Immunology; Professor, Molecular Immunology, Centre for Cancer Immunology, University of Southampton


Engineering Therapeutic Antibodies for Conditional Activation of Antigen Binding and Effector Functions

Harald Kolmar, PhD, Professor and Head, Institute for Organic Chemistry and Biochemistry, Technische Universität Darmstadt

We have generated a series of conditionally masked therapeutic antibodies that are unmasked in the tumor microenvironment by acid pH and/or by proteolytic removal of the masking entity. Using anti-idiotype shark-derived vNARs, pH-responsive paratope binders were generated by yeast display screening. As an additional broadly applicable approach to modulate effector functions of IgG1 therapeutic antibodies, a protease-cleavable Fc-masking scFv was developed, efficiently blocking Fc-gamma receptor binding conditionally.


Generation and Engineering of Mono- and Bispecific Cattle-Derived Ultralong CDR-H3 Antibodies by Yeast Surface Display

Stefan Zielonka, PhD, Director, Protein Engineering & Antibody Technologies Discovery Technologies, Global Research and Development, Merck KGaA

A subset of antibodies found in cattle comprises ultralong CDR-H3 regions of up to 70 amino acids. These peculiar entities display a huge structural diversity that makes them attractive for biomedical applications. We have generated a robust platform process to specifically harness this subset after immunization. Moreover, we have engineered bispecific common-light-chain antibodies based on ultralong CDR-H3 diversities and demonstrated that these molecules are versatile for conditionally activating NK cells.

12:15 Targeting the High-Hanging Fruit - Icosagen Therapeutics Antibody Development Pipeline

Siret Tahk, PhD, Senior Researcher, Icosagen Cell Factory

Multi-pass integral membrane proteins compose the largest therapeutically relevant group of proteins that have so far not been effectively targeted with antibody-based molecules. Icosagen has developed a wide array of expertise and technologies in protein production, antibody development, protein engineering and analytics over the past 10 years and here we present the integration of these technologies by launching our therapeutic antibody development pipeline to specifically target those proteins.

Session Break12:45

12:55 Writing the Future of Biologics with Synthetic DNA and Machine Learning

Aaron Sato, PhD, Chief Scientific Officer, Twist Bioscience

Utilizing its proprietary DNA technology to write synthetic libraries, Twist Biopharma provides end-to-end antibody discovery libraries including highly diverse, synthetic, naïve antibody phage display libraries and target class specific antibody phage display libraries against difficult-to-drug targets.  Here, Aaron will cover how Twist uses these libraries coupled with Machine Learning to discover 1) antibody sequences from NGS sequencing of our successive panning rounds and 2) optimize existing leads derived from traditional screening.

13:25 Concurrent use of Humanized and Hyperimmune Mice for Rapid, Function-Forward mAb Discovery

Ryan Kelly, Head, Business Development, In Vivo Antibody Discovery Services, Business Development, Abveris, A Division of Twist Bioscience

Leveraging the natural immune repertoire for antibody discovery has distinct advantages for positive downstream outcomes; however, conventional antibody screening methodologies typically fail to provide the throughput and resolution required to thoroughly mine the full genetic diversity in these in vivo workflows. In this presentation, Abveris will discuss some strategies for overcoming these challenges in the context of a case study highlighting a discovery campaign against a notoriously intractable cell surface receptor.

Session Break13:55



Chairperson's Remarks

Joao Goncalves, PhD, Full Professor, Microbiology & Immunology, University of Lisbon


A Bench-to-Bedside Phenotypic Discovery Approach Identifies Anti-FcgRIIB as a Promising Strategy to Overcome Antibody Drug Resistance

Björn L. Frendeus, PhD, CSO, BioInvent International AB

We used a phenotypic discovery approach comprising differential antibody display screening of primary leukaemic B cells and healthy donor PBMCs to identify antibodies and targets associated with direct and immune effector cell-mediated killing of leukaemic B cells.  The inhibitory FcγRIIB was identified as a promising target. Anti-FcγRIIB overcame rituximab resistance in vivo and is currently being trialed in clinical Phase I/II trials with relapsed/refractory NHL patients.


Deploying Antibody Fragments inside Cells for Phenotype Modulation and Drug Discovery in Cancer

Terence Rabbitts, FRS, FMedSci, Professor, Molecular Immunology, Center for Cancer Drug Discovery, Institute of Cancer Research

Chromosomal translocation-proteins and mutant RAS are among hard-to-drug proteins in cancer. Intracellular antibodies are a starting point as inhibitors via design to block protein-protein interactions or to carry effector functions. Fusion with E3 ligases creates bio-degrader intracellular antibodies to eliminate target proteins. The effect of bio-degraders targeting LMO2 and mutant RAS on cancer cells will be discussed and approaches to establish delivery of intracellular antibodies as drugs per se.


Selection and Characterization of Cell Binding and Internalizing Anti-Nucleolin Antibodies

Joao Goncalves, PhD, Full Professor, Microbiology & Immunology, University of Lisbon

New nucleolin-targeting nanobodies with cytotoxic activity against nucleolin-overexpressing breast cancer cells were developed. The nanobody-Fc antibody presented nucleolin-mediated ADCC capacity. Antibodies were optimized by random mutagenesis in E. coli and selected by endocytic properties by flow cytometry. The best nanobody candidates presented a single mutation in CDR3 and showed increased potency. Data will be presented on the optimization and biologic activities of selected anti-nucleolin antibodies.

15:50 Effectively Meeting Today’s Antibody Discovery Needs: Methods to Address Narrow Diversity Targets and Functionality

Pavel Pitule, PhD, Vice President Discovery, AbCheck s.r.o.

Novel technology solutions are needed to overcome the challenges of today’s drug discovery and development. In particular, tailored solutions beyond antibody-antigen binding affinity criteria are required for the discovery of therapeutic antibodies with challenging Target Product Profiles (TPPs). AbCheck’s customized microfluidics solutions address these challenges by meeting the key requirements for potent, function-specific antibodies and enabling functional screening of millions of single cells/day.

Refreshment Break in the Hall with Poster Viewing (Verdi and Vivaldi 1&2)16:20


Measuring Antibody-Antigen Interactions at a Library-on-Library Scale Using a Yeast Display Platform to Discover and Optimize Antibodies with Defined Specificity and Cross-Reactivity Profiles

David A. Younger, PhD, Co-Founder & CEO, A Alpha Bio

Current antibody discovery and optimization methods reliably produce strong binders to the immunodominant epitopes of most targets by enriching for a single property: target affinity. However, therapeutic antibodies require multi-variable optimization for binding to target(s), animal orthologues, paralogues, related proteins, and other human proteins – as well as optimization for developability. Here, we will demonstrate how multi-dimensional antibody-antigen protein interaction datasets generated using the AlphaSeq platform enable the discovery and optimization of antibodies to diverse target epitopes with desired specificity and cross-reactivity profiles. In addition to direct selection of antibodies with desirable binding properties, AlphaSeq data is used to train machine learning models to improve the speed and quality of subsequent antibody designs.​


Display Developments for Bench-to-Bedside Applications


Ahuva Nissim, PhD, Professor, Antibody and Therapeutic Engineering, William Harvey Research Institute, Queen Mary University of London

E. Sally Ward, PhD, Director, Translational Immunology; Professor, Molecular Immunology, Centre for Cancer Immunology, University of Southampton


Fortunato Ferrara, PhD, Vice President, Discovery Services, Discovery, Specifica Inc

Harald Kolmar, PhD, Professor and Head, Institute for Organic Chemistry and Biochemistry, Technische Universität Darmstadt

Stefan Zielonka, PhD, Director, Protein Engineering & Antibody Technologies Discovery Technologies, Global Research and Development, Merck KGaA

Welcome Reception in the Exhibit Hall with Poster Viewing18:05

Close of Display of Biologics Conference19:05