Cambridge Healthtech Institute’s Inaugural
Engineering Antibodies

Inspiring Next-Generation Biologics Discovery and Development

2 - 3 November 2016 | EPIC SANA Lisboa Hotel | Lisboa PORTUGAL

One of the top imperatives for protein engineers is to identify novel drug targets, screen and select the right antibodies, and engineer the antibodies to improve the targeting, specificity and clinical effectiveness against the targets. The Inaugural Engineering Antibodies at PEGS Europe will explore the state-of-the-art tools and technologies for target discovery and validation, antibody selection and screening, as well as engineering strategies to improve the targeting of antibody therapeutics. Scientists in the field will share case studies and to-be-published work to inspire the next generation of protein engineers in their discovery and development of next-generation biotherapeutics.

Final Agenda

Day 1 | Day 2 | Speaker Biographies | Download Brochure

WEDNESDAY 2 NOVEMBER

07:45 Registration and Morning Coffee

TECHNOLOGIES AND STRATEGIES TO IMPROVE TARGETING AND BIOACTIVITY OF THERAPEUTICS

08:30 Chairperson’s Remarks

Claudio Sustmann, Ph.D., Head, Molecular Design & Engineering, Large Molecule Research, Roche Diagnostics GmbH

09:20 Protease-Activated Antibody Derivatives - Engineered bsAbs with Prodrug-Like Functionality

Ulrich Brinkmann, Ph.D., Expert Scientist, Large Molecule Research, Roche Pharma Research & Early Development

Bispecific and engineered antibody derivatives have been generated in a multitude of formats. Many of these are in preclinical stages for a variety of applications, some in clinical development, and a few are approved. The presentation will provide an overview of the concepts and status of engineered bispecific antibodies at Roche and cover novel formats and applications including bispecific antibody derivatives with prodrug-like functionalities.

09:50 Characterizing and Optimizing Glycostructures by Targeted Cell Engineering

Claus Kristensen, Ph.D., Associate Professor, Copenhagen Center for Glycomics, University of Copenhagen

Using targeted gene editing of mammalian cells we modify sugars on glycoproteins. The technology involves knock-out and/or knock-in of glycogenes to modify cellular glycosylation pathways and generate arrays of different glycans on glycoproteins produced by the cell. Application includes glycooptimization of biologics for improving bioactivity and/or obtain more homogeneous product.

10:20 A Deimmunised Form of the Ribotoxin, α-sarcin, Lacking CD4+ T Cell Epitopes and Its use as an Immunotoxin Warhead

Rob Holgate, Ph.D., Head, Protein Engineering, Abzena

Fungal ribotoxins that block protein synthesis are useful warheads. Peptide mapping using an ex-vivo human T cell assay determined that α-sarcin contained two T cell epitopes. Mutations within each epitope were designed, tested and combined to isolate deimmunised α-sarcin variants with the desired properties of silencing T cell epitopes whilst retaining the ability to inhibit protein synthesis. The results represent the first fully deimmunised fungal ribotoxin.

10:50 Coffee Break in the Exhibit Hall with Poster Viewing

11:30 Highly Efficient Elimination of High Concentration Soluble Antigen from Plasma by Novel Sweeping Antibody Technology

Meiri Shida-Kawazoe, Ph.D., Research Scientist, Biologics Discovery, Chugai Pharmaceutical Co., Ltd.

In this presentation, we will introduce novel sweeping antibody technology that enables highly efficient elimination of soluble antigen from plasma. The novel technology has been applied to various antigens, which are present at high concentration in plasma and therefore difficult to target by conventional antibodies, and we will show that these antibodies can efficiently eliminate various soluble antigens from plasma in cynomolgus monkey.

12:00 Antibody Engineering in Drug Discovery & Development at Roche

Claudio Sustmann, Ph.D., Head, Molecular Design & Engineering, Large Molecule Research, Roche Diagnostics GmbH

Bispecific antibodies are an important drug class in oncology but also beyond. Identification of the best candidates for a certain application is a challenging task. These aspects as well as selected examples of Roche development candidates will be the focus of the presentation. In particular, application of the IgG-like bispecific CrossMab technology in different disease areas will be addressed.

12:30 Rapid Affinity Measurements Using Gyrolab Immunoassay Platform

Johan Engström, Senior Scientist, Research & Development, Gyros AB

Real-time, surface-based analytical methods often have difficulty in analyzing the slow dissociation kinetics associated with high-affinity KD’s. Gyrolab systems enable rapid determination of KD’s down to low picomolar levels. This will be illustrated with the KD determination for three TNF-a antagonists and the active binding concentration of the antagonists.

12:45 Antibody Protein De Novo Sequencing with LC-MS/MS

Mingjie Xie, MSc, MBA, Co-Founder, 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.

13:00 Luncheon Presentation: A New Strategy to Screen Clones from Phage Display at Early Stages by Kinetic Affinity Study

Marie Gagnaire, Research Scientist, Protein Biochemistry, Biologics Research, Sanofi

13:30 Session Break

ANTIBODY DISCOVERY FOR EMERGING AND CHALLENGING TARGETS

14:00 Chairperson’s Remarks

Claus Kristensen, Ph.D., Associate Professor, Copenhagen Center for Glycomics, University of Copenhagen

14:05 Efficient Mining of the Natural Antibody Repertoire – Finding Rare Molecules with Desirable Characteristics

Dale Starkie, BSc., Research Scientist, Antibody Discovery, UCB Celltech

UCB’s core antibody discovery technology combines high throughput B cell culture screening and a proprietary technique called the “fluorescent foci method” to identify and isolate single, antigen-specific, IgG-secreting B cells from which variable region genes are isolated and cloned. The talk will describe case studies on the application of the platform to a number of antibody projects.

14:35 Discovering Antibodies to a Moving Target

Elizabeth England, Scientist I, Antibody Discovery and Protein Engineering, MedImmune Ltd.

MedImmune has shown that IL-33 forms disulphide bonds, resulting in large conformational changes. This occurs rapidly, posing a challenge in identifying antibodies that inhibit the action of IL-33. Through innovative use of mutant forms of IL-33 and appropriate design of screening campaigns, a highly potent inhibitor of IL-33 was identified, a testament to how understanding of target structure and biology is key to the identification of potential therapeutic drug candidates.

15:05 Antibodies Targeting Peptide/HLA Complexes for Cancer Therapy

Julia Neugebauer, Ph.D., Associate Director/Leader, Discovery Programs, Morphosys AG

Tumor-specific peptide / HLA complexes make intracellular targets accessible to antibodies. However, the generation of therapeutic antibodies, which recognize a particular peptide / HLA complex specifically, is highly challenging. By identifying and applying appropriate counter-targets we generated fully human, high affinity antibodies against a WT1 peptide / HLA complex. These antibodies bind to target-positive cancer cell lines and outperform similar state-of-the-art antibodies regarding target specificity and binding affinity.

15:35 Refreshment Break in the Exhibit Hall with Poster Viewing

16:15 Strategies to Identify High Potency Therapeutic Antibodies for Multi-TM Targets 

Peter Ertl, Ph.D., Manager, Biopharm Molecular Discovery, GlaxoSmithKline

Cellular targets such as G-protein coupled receptors (GPCRs) are typically very challenging for therapeutic antibody discovery due to their complex nature and limited antigen availability. This presentation will describe the strategies implemented by GSK to successfully identify high potency neutralising antibodies for such targets, using both in vitro antibody presentation technologies and in vivo immunisation approaches.

16:45 Integration of High Throughput Omic’s Platforms into Antibody Discovery

John Castle, Ph.D., Senior Director, Bioinformatics, Agenus & 4-Antibody

In pursuit of lead structures, omic technologies are revolutionizing the discovery and development of novel biological lead structures. However, omic platforms are first and foremost data generation instruments that require careful integration into workflows. Here, we demonstrate how we have applied next-generation sequencing, big data, biostatistics, and computational immunology to the discovery and development of novel antibody lead structures.

18:15 Networking Reception in the Exhibit Hall with Poster Viewing

19:15 End of Day

Day 1 | Day 2 | Speaker Biographies | Download Brochure

THURSDAY 3 NOVEMBER

08:00 Registration and Morning Coffee

COMPUTATIONAL AND IN SILICO DESIGN AND ENGINEERING

08:30 Chairperson’s Remarks

David Melvin, Ph.D., Director, Informatics, Kymab Limited

08:35 Engineering Protein-Protein Interactions in silico: Lessons from the Affibody Scaffold

Samuel Coulbourn Flores, Ph.D., Group Leader, Structural Bioinformatics and Computational Structural Biology, Uppsala Universitet

Altering protein-protein interface properties is key to biologic design, but experimental directed evolution introduces many mutations, leading to immunogenicity and off-target effects. We have created an in silico method which predicts single mutations with a clear mechanism, to modify charge and binding properties and remove functionalization sites. We engineer properties of the Affibody – IgG interaction. I briefly discuss how to apply this to important oncology and autoimmune disease targets.

09:05 Beyond Binding: How to Design Biologically Active, Developable Antibodies against Difficult Targets

Yanay Ofran, Ph.D., Founder & CEO, Biolojic Design; Head, Lab of Systems Biology and Funcional Genomics, Bar Ilan University

It is fairly straightforward to obtain antibodies that specifically bind almost any protein. However, further screenings and analyses typically reveal that most of these binders are not biologically active or not developable. This is because existing methods for antibody engineering select for binding, while drug development requires function and developability. We show how computational design and in vitro evolution can be combined to design developable antibodies with specific, predefined function.

09:35 Rational Design of Antibody Solubility and Complementarity Determining Regions

Pietro Sormanni, Ph.D., Researcher, Chemistry, Centre for Misfolding Diseases, University of Cambridge

I will present a computational strategy for the design of soluble binding proteins as well as experimental validations and applications. I will introduce the CamSol method of designing protein variants with improved solubility, and a method for the de novo design of protein-protein interactions, which we used to design domain antibodies and molecular-chaperones binding to linear epitopes and able to inhibit the disease-related aggregation of their target proteins.

10:05 Engineering Next-Generation Biotherapeutics: Developability & Manufacturability

Maria Wendt, Ph.D., Head, Science, Biologics, Genedata

Next-generation biotherapeutics, specifically bi- and multi-specifics, alternative scaffolds, and ADCs, provide significant advantages over traditional IgG-based molecules. However, as highly engineered molecules they pose new design, cloning, expression, purification, and analytics challenges. Our workflow platform automates engineering, production, and testing of large panels of these candidate therapeutic molecules. We demonstrate the platform’s capability to explore the huge combinatorial space of novel molecule-specific designs, its high-throughput capability, and its built-in tools for developability and manufacturability assessments.

10:35 Coffee Break in the Exhibit Hall with Poster Viewing

HIGH THROUGHPUT SCREENING AND SELECTION

11:15 High-Throughput Screening of Monoclonal Antibodies to Multiplexed Antigens

Benjamin Hoffstrom, Ph.D., Director, Antibody Technology, Fred Hutch Cancer Research Center

We have a high-throughput platform for simultaneous screening of monoclonal antibodies to 5 different antigens. The target identification assay is 25-50 times more sensitive than traditional ELISA-based screens, which allows for rapid ranking of several thousand antibodies based on target affinity and isotype. We have validated the platform for modified peptide targets, small molecules, recombinant proteins, and cell surface receptors. A general overview of the workflow will be outlined and specific projects will be highlighted.

11:45 Advances in Kymab’s Fully Integrated, B-Cell Repertoire Analysis and Hit Selection Capabilities

David Melvin, Ph.D., Director, Informatics, Kymab Limited

Kymab have developed an advanced technology to visualise and deeply explore the Kymouse™ antibody repertoire. We can identify candidate-quality molecules with exceptionally broad diversity and with the quality of fully human antibodies. Our platform allows rapid, detailed and efficient exploration of the B-cell response to immunisation as well as informing and supporting decision making process throughout our discovery program. We will present our work with the Bill and Melinda Gates foundation.

12:15 Luncheon Presentation: Generating More Relevant Data: High Titer Antibody Production in a Range of Host Cells using Scalable Electroporation

Payal Roychoudhury, Ph.D., Field Applications Scientist, EU, MaxCyte, Inc.

One aspect of lowering costs and reducing attrition rates during biotherapeutic development is the ability to work in the cell line of choice during early-stage discovery. In this presentation, we demonstrate the ability of MaxCyte electroporation to produce high antibody titers in a variety of CHO cell lines. Additionally, the production of CHO antibody titers >2.7 g/L and the seamless scalability of MaxCyte electroporation are presented as well as analysis of protein quality and glycosylation patterns.

13:00 Dessert Break in the Exhibit Hall with Poster Viewing

13:30 End of Engineering Antibodies

Day 1 | Day 2 | Speaker Biographies | Download Brochure

Conference Programs

• Display of Biologics
• Engineering Antibodies
• Machine Learning - Part 2

• Antibody-Based Therapies
• Emerging Targets & Approaches
• Membrane Protein Targets

• Safety & Efficacy
• Advancing Bispecifics
• Engineering Bispecifics

• Modulating the TME
• Innovative CAR T Therapy
• Next-Gen Immunotherapies

• Optimisation & Developability
• Analytical Characterisation
• Protein Stability & Formulation

• Data Science & Engineering
• Optimising Expression
• Process Development

• Intro to Machine Learning
• Machine Learning - Part 1
• Machine Learning - Part 2

• Antibody-based Therapies
• Engineering Conjugates
• Clinical Success in ADCs