Original Agenda
We are actively working with our speakers to confirm their availability for the virtual event. Initial response from our speakers has been very positive, and we are optimistic we will have the new programs ready to share here soon.

Optimisation & Developability track banner

The Optimisation & Developability program reviews innovative approaches, methods and models that scientists use to develop strategies for candidate selection, safety and efficacy prediction, liability mitigation, and developability assessments; at the same time presents optimisation strategies to improve affinity and activity. The conference will also explore the applications of machine learning and in silico approaches to predict developability and manufacturability.

Monday, 9 November

08:00 Short Course Registration
09:00 Recommended Short Course*
SC4: Preclinical Models for Cancer Immunotherapy

*Separate registration required. See short course page for details.

12:00 Conference Registration

DEVELOPABILITY ASSESSMENT AND ADVANCING CANDIDATES

13:30 Welcome by Conference Organizer

Mimi Langley, Senior Conference Director, Cambridge Healthtech Institute

13:35

Chairperson's Opening Remarks

Charlotte M. Deane, PhD, Professor of Structural Bioinformatics, Statistics, University of Oxford
13:45 KEYNOTE PRESENTATION:

Towards ML-Enabled Antibody Drug Discovery at Bayer: Vision and Step-Wise Approach

Philipp Ellinger, Dr rer nat, Lab Head, Analytical Biochemistry, Biologics Research, Cell, Gene and Protein Sciences, Bayer AG

I will present Bayer's vision on how to perform in-house antibody lead discovery, and select from there the best candidates for further assessment as therapeutic candidates supported by machine learning approaches. It will be a concept supplemented with first small-use cases.

14:15 Case Study of EGFR-cMET Molecule Now in Late-Stage Development
Mark L. Chiu, PhD, Associate Director, Development, Janssen Research
  • Strategy for process optimization
  • Need to determine and understand the critical quality attributes and to develop assays for the quality attributes
  • Need for understanding the various Modes of Action of the molecule
  • Demonstration of process control to the regulatory authorities to avoid the all-to-common failure in phase 3
  • Pitfalls to avoid and challenges overcome
14:45

Developing Precision TCR-Like Specificities Using the NextCore Phage Display Platform

Geir Age Loset, PhD, CEO, Nextera AS

To identify and develop optimal lead candidates against specific members of the HLA ligandome remains difficult. We have used a combination of classical HLA-matched subtractive antibody phage display in combination with thermal and competitor challenged CDR and FR targeted engineering using our pIX-based NextCore display platform to develop highly specific TCR-like antibodies allowing for high-resolution T cell epitope targeting and sequestering.

Nena Matscheko, PhD, Scientist – Team Lead Cell Applications, Dynamic Biosensors GmbH

switchSENSE® tackles the challenge of quantifying association and dissociation rates of antibodies in their native environment. The new heliX Biosensor delivers in vitro data on target and off-target kinetic rates measured on cell surfaces with defined epitope distributions. Multiplexed resolution of affinity and avidity speeds up development of your bi- and multi-specific, or locked, formats.

15:45 Networking Refreshment Break

PLENARY KEYNOTE SESSION

16:15

Keynote Chairperson's Remarks

Denise L. Faustman, MD, PhD, Associate Professor & Director, Immunobiology Labs, Massachusetts General Hospital
16:20 Learning from What Works: Dissection of Successful Cancer Clearance by the Immune System
Andrew Sewell, PhD, Distinguished Research Professor and Wellcome Trust Senior Investigator, Division of Infection and Immunity, Cardiff University School of Medicine

What is the key to success? How do some rare patients spontaneously clear extreme cancer? What is being recognised by T cells during successful tumour-infiltrating lymphocyte or T cell checkpoint therapy? We have developed two new methodologies that allow rapid determination of the ligand recognised by any ‘orphan’ T cell clone. These techniques have enabled us to address these questions and discover novel cancer-associated epitopes expressed by most cancers.

17:05

mAbs vs. Bugs: Antibody Therapies for Infectious Disease

Steve Martin, PhD, Vice President, Biopharm Discovery, GlaxoSmithKline

This year’s coronavirus pandemic has provided a stark reminder of the threat to global health posed by infectious disease and the need for new treatments. Renewed attention has been brought to the potential of antibodies as anti-infective therapeutics, which historically has been a challenging area for drug discovery. Synergies between modern vaccine development approaches and antibody discovery technologies offer new opportunities in the fight against our microbial foes.

17:50 Welcome Reception in the Exhibit Hall with Poster Viewing
19:00 End of Day

Tuesday, 10 November

07:45 Registration and Morning Coffee

COMPUTATIONAL AND PREDICTIVE APPROACHES TO DEVELOPABILITY AND OPTIMISATION

08:30

Chairperson's Opening Remarks

Max Vasquez, PhD, Vice President, Computational Biology, Adimab LLC
08:35 Humanization of Antibodies Using a Machine Learning Approach
Charlotte M. Deane, PhD, Professor of Structural Bioinformatics, Statistics, University of Oxford
09:05 An in silico Perspective of the Therapeutic Antibody Landscape
Max Vasquez, PhD, Vice President, Computational Biology, Adimab LLC

We will review published examples where antibody developability metrics were assessed on large antibody sets and sequence information provided.  We will apply existing and in-development computational approaches aimed at assessing some of those metrics from sequence information alone.

09:35 Molecular Decomposition of Polyclonal Immunoglobulin Repertoires
Gregory C. Ippolito, PhD, Research Assistant Professor, Molecular Biosciences, University of Texas at Austin

Traditional antibody discovery typically investigates membrane-bound antigen-receptors encoded by a pool of B cells. Alternatively, mass spectrometry can identify high-affinity, bioactive antibody proteins secreted by a select subset of the total B-cell pool. Here, I present: (i) two techniques which can comprehensively determine cellular and serological antibody repertoires; and (ii) data illustrating the connectivity between them in the context of two primary immune responses–malaria vaccination and SARS-CoV-2 infection.

10:05 Problem Solving Breakout Discussions*

*Topics to be announced.

10:30 Coffee Break in the Exhibit Hall with Poster Viewing
11:15

Early in silico and in vitro Screening for Improved Biophysical Properties of Antibodies and Bispecific Antibodies

Patrick Farber, Scientist, Technology Intergration, Zymeworks Inc.

In the development of an antibody therapeutic, candidates are often chosen for their desired functional properties rather than their stability and manufacturability. This talk will describe the use of rational design of a bispecific antibody to improve properties including heterogeneity, stability, and purity. Additionally, I will present predictive in-vitro and in-silico developability techniques for early detection of liabilities that can affect biological function, clearance, and homogeneity.

11:45

From Glassware to Software: Better Understanding of Chemical Degradation Mechanisms by Physics-Based Simulations

Saeed Izadi, PhD, Scientist, Early Stage Pharmaceutical Development, Genentech, Inc.

Aspartate isomerization and asparagine deamidation are spontaneous post- translational modifications that adversely affect therapeutics function and long-term stability. In this talk, I will present a comprehensive analysis of 1000+ isomerization and deamidation sites across 130+ antibodies. A total of ~500 microsecond, unrestrained molecular dynamics simulations, along with extensive quantum mechanics (QM) calculations at the peptide level, were utilized to understand the mechanistic roles of structure and chemical environment promoting the isomerization and deamidation reaction. Such physics-based classification models require no heavy training against the data set, thus they can be leveraged to predict deamidation and isomerization propensity of therapeutic proteins in external data sets.

13:15 Luncheon Presentation II (Sponsorship Opportunity Available)
13:45 Dessert Break in the Exhibit Hall with Poster Viewing

OPTIMISATION STRATEGIES FOR IMPROVED AFFINITY, ACTIVITY AND DEVELOPABILITY

14:15 Chairperson's Remarks

Annika Schmid, PhD, Associate Director, MorphoSys AG

14:20

Display-Based Approaches for Antibody Developability Optimization

Orla Cunningham, PhD, Senior Director, Biomedicine Design, Pfizer Inc.
14:50 Optimising C7 Antibodies for High Affinity and Developability
Susannah Davis, Scientific Leader, BioPharm, GlaxoSmithKline

Focusing antibody engineering and selection strategies towards the isolation of high-affinity molecules can sometimes come at the expense of a robust developability profile. Incorporating strategies to optimise both affinity and biophysical characteristics during the discovery phase is important in ensuring that we develop high-quality, safe, and efficacious drugs. In this presentation, we will describe the methods that we applied to improve the affinity and developability attributes of a diverse panel of C7 antibodies. Affinity improvements were engineered using CDR-targeted mutagenesis libraries constructed in the Adimab Yeast Platform. In parallel, developability liabilities were removed using molecular design and engineering approaches combined with early quality-based screening techniques.

15:20 Predicting Solution Behavior during Developability Screening
Charles G. Starr, PhD, Scientist, Developability & Preformulation Sciences, Sanofi Group

Early-stage developability assessments of biologic drug candidates are often undertaken with minimal material availability. Such resource limitations complicate or prevent completely the characterization of macroscopic solution properties, such as viscosity and opalescence, which only emerge at high protein concentrations. Here, we present a strategy for the identification of molecules with a high propensity to self-associate in dilute solution, which is strongly predictive of poor solution behavior at elevated concentrations.

15:50 Sponsored Presentation (Opportunity Available)
16:20 Refreshment Break in the Exhibit Hall with Poster Viewing
17:00

Antibodies against Complex Molecules

Annika Schmid, PhD, Associate Director, MorphoSys AG

Methods generating highly specific antibodies against classical target molecules, as e.g., receptor tyrosine kinases or cytokines, are routinely established. Antibody compounds inhibiting these classical target classes are widely used in clinical development and as approved therapeutics. Innovative selection strategies like next-generation sequencing have been applied to enable broadening the target space and addressing new target classes such as e.g., HLA/peptide complexes.

17:30

Determining Binding Affinities of Therapeutic Antibodies Targeting Transmembrane Proteins

Tony Christopeit, PhD, Research Scientist, Pharma Research & Early Development, Roche Diagnostics GmbH

Investigating the interaction of antibodies with membrane proteins under physiologically relevant conditions is a challenging task. We have explored different methods, such as surface plasmon resonance (SPR)-based biosensors, Ligand Tracer and KinExA, to investigate the interaction of antibodies with full-length membrane proteins embedded into a lipid membrane. The assays allowed the calculation of binding affinities (KD), and hence improved the assessment of therapeutic antibodies.

18:00

Presence of a Positive Charge Cluster on Fc-fusion of Mouse LIGHT Impacts Its Exposure and in vivo Activity in Mice

Ayse Meric Ovacik, PhD, Scientist, Developmental Sciences, Genentech, Inc.

Mouse LIGHT (targeting the Lymphotoxin beta receptor, LTBR) showed significant PK liability in mice, therefore in vivo studies could not be interpreted. Homology modeling identified a positive charge cluster on the mouse ligand. We engineered two alternative variants where the cluster was removed. The variants showed no impact on the binding and in vitro activity with substantial improvement in exposure, and an increase in Ccl19 (biomarker for agonizing LTBR pathway). We will present novel work, where an interdisciplinary scientific team (structural biology, protein chemistry, pharmaceutical science, and immuno-oncology) synergistically improved the therapeutic potential of a Fc-fusion protein.

18:30 Close of Optimisation & Developability