EAC 2017 Day 3, Thursday 2nd November 2017

08:00 Registration Opens

08:50 Conference doors open

Keynotes – World leading research

Sir Gregory Winter
09:05

Keynote: Bicycles - a paradigm shift in pharmaceutical drugs?

  • New platform based on repertoire technology
  • Peptide conjugates with toxic drugs for treatment of cancer
 
Prof. Andreas Plueckthun
09:30

Keynote: Future Biologics: Exploiting the opportunities for protein engineering

  • Future biologics need to open areas of application that expand on today’s possibilities. This will be illustrated in several key areas
  • The possibility of engineering geometry can be used to exert extremely strong effects on receptor signalling, such as a pan-HER inhibition
  • Intracellular targets may gradually come within reach. Using systems inspired by engineered bacterial toxins (3), levels can now be reached which are much higher than with positively charged peptides, and more importantly, allow cell-specific uptake
  • Viral delivery may open new avenues to administer cocktails of therapeutic proteins in a localized manner, not by creating replication-proficient “oncolytic” viruses, but instead by engineering viruses, able to target predesigned cell types (5), which can be used to produce therapeutic proteins in vivo, at locations where they are needed
 
Dr Christoph Rader
09:55

Keynote: Cancer therapy with antibodies at the interface of biology and chemistry

  • The presentation will encompass two strategies on covalently combining antibodies with small molecules to improve their scope and potency
  • One strategy employs homogeneous antibody-drug conjugates that selectively deliver highly toxic small molecules to cancer cells without harming healthy cells
  • The other strategy is based on chemically programmed bispecific antibodies that endow cancer-targeting small molecules with the power of cancer immunotherapy
 
Dr M. Anthony Moody
10:20

Keynote: Immune regulation and the antibody response to HIV-1

  • Many antibodies that have potent activity against HIV-1 have characteristics of autoantibodies
  • Infected persons who make those antibodies have Immune system perturbations suggestive of dysregulation
  • Understanding the relationship between immune dysregulation and HIV-1 antibody responses may help guide vaccine design
 

10:45 Networking Break

Target distribution

Novel antibody technologies and future uses

mAbs

Chaired by Carl Webster, Principal Scientist, Antibody Discovery and Protein Engineering, MedImmune

Chaired by Stefan Dübel, Director, Department of Biotechnology, Technnische Universität Braunschweig

Chaired by Sai Reddy, Assistant Professor, Biomolecular Engineering, ETH Zurich

11:45

Antibody therapeutics for CNS diseases and their delivery across the BBB

  • We have used our antibody engineering platform to develop a fully human monoclonal antibody that crosses the blood brain barrier and an antibody that blocks the ligand gated ion channel P2X4
  • We have confirmed central penetration and PK of the BBB antibody in vivo
  • We have utilised a model of neuropathic pain to confirm activity of the P2X4 antibody in a bi-specific construct with the BBB antibody
 
11:45

Universal affinity switches for antibodies

  • Allosteric affinity modulation module for scFv antibodies
  • Demonstrated to switch 5 different antibodies
  • Works both for Vl-Vh and Vh-Vl scFv
  • Works at physiological milieu (no ph / ion changes necessary)
 
11:45

Targeting netrin-1: from preventing cancer stemness to strengthening immunotherapy

  • Overview on dependence receptors
  • The pairs netrin-1/netrin-1 receptors (DCC, UNC5B) are the prototypical ligand/dependence receptors pairs
  • An anti-netrin-1 mAb called NP137 has been preclinically developed and is currently assessed in a first-in-man-first-in-class phase I clinical trial
  • The NP137 shows preclinical efficacy related to a specific effect on cancer stem cells.
  • Preclinical data support the importance of combining NP137 with immune-checkpoint inhibitors. 
 
12:05

Optimizing delivery of antibodies across the BBB via the Transferrin Receptor and other novel transporters

  • We have developed second generation single domain VNARs for efficient transfer of antibodies across the BBB
  • Using a combined in Vitro and in Vivo phage display screening paradigm we have isolated VNARs to the transferrin receptor that give brain /plasma ratios of up to 10% at 20 hours with clear parenchymal staining
  • Mutagenesis of the VNAR CRD3 region has identified key residues essential for transfer and allowed additional optimization
  • New non TfR VNARs have been isolated from in Vivo phage display with highly efficient transfer. Current efforts are designed to identify the molecular targets
 
12:05

Antibodies to post translationally modified auto-antigens as biomarker for early diagnosis of disease

  • Link between metabolism and autoimmunity
  • Formation of neoantigen at early stages of autoimmune diseases
  • Examples from arthritic conditions and Type 1 autoimmune diabetes
 
12:05

Discovering and engineering antibodies by high-throughput repertoire sequencing

  • Computational and experimental methods in antibody repertoire sequencing
  • Comprehensive error and bias correction method that enables highly accurate sequencing
  • Applying machine-learning approaches that enable prediction of the immune status
  • Use of genome editing and mammalian cells to screen antibody repertoires
 
12:25

Blood-brain barrier penetrating dual specific binding proteins for treating brain and neurological diseases

  • Will describe the generation and expression of DVD-Ig proteins which are capable of binding specific disease targets in the brain.
  • The brain uptake and retention, following an systemic administration, as well as the elevated functional activity of DVD-Ig proteins will be demonstrated.
 
12:25

Novel microbial fermentation technology for production of antibodies

  • Cost and time efficient development of microbial fermentation
  • Controlled regulation of expression yields in E. coli
  • Case study: E. coli as platform for production of functional antibody fragments
 
12:25

Anti-stem monoclonal antibodies against Influenza

  • Neutralization and ADCC are the mechanisms of broadly cross-reactive protection provided by monoclonal antibodies against the stem region of Influenza HA antigens
  • Stem directed monoclonal antibodies protect broadly protect in the mouse and ferit against influenza challenge
  • Human influenza challenge studies demonstrate that higher levels of these monoclonal antibodies are required in the nasopharynx for protection than can practically by achieved by intramuscular injection
  • Active vaccines have been designed based on the epitopes identified by these monoclonal antibodies that can elicit broad neutralizing antibody, ADCC and protection in the mouse lung
 
12:45

Liver targeted insulin

  • Design and generation of an antibody based liver biased insulin analog
  • The construct showed enhanced insulin activity on hepatocytes in vitro
  • The construct demonstrated liver biased distribution and PD effect in rats
 
12:45

Droplet microfluidics – antibody discovery and vaccine development at very high throughput

  • Droplet based microfluidics for the direct screening and sequencing of millions of primary murine (from spleen and bone marrow) and human (from blood) plasma cells
  • Assays for antibody binding, inhibition of enzymatic drug targets, effect on target cells
  • Compatible with difficult targets such as GPCRs
  • Complementary platform for the development of vaccine candidates based on massively parallelized single-virus assays
 
12:45

LY2624587, a clinically tested anti-CXCR4 antibody induced apoptosis of hematologic malignancies

  • Overexpression of CXCR4, a receptor for the chemokine CXCL12 (SDF-1), is a hallmark of many haematological malignancies including acute myeloid leukaemia, chronic lymphocytic leukaemia and non-Hodgkin’s lymphoma, and generally correlates with a poor prognosis.
  • We developed and advanced into the clinic, a potent anti-CXCR4 monoclonal antagonist antibody, LY2624587, for treatment of cancer
  • LY2624587 blocked SDF-1 binding to CXCR4 and inhibited SDF-1 induced cell migration and downstream cell signalling
  • In human hematologic cancer cells, LY2624587 caused dose dependent apoptosis in vitro and in vivo
 
13:05

Recombinant antibody brain shuttles - Improved immunotherapy and diagnostics of neurodegenerative diseases

  • We have generated a shuttle that transports antibodies across the BBB
  • It is bivalent but binds monovalently to the TfR dimer
  • We have used it to improve antibodies in both diagnostics and therapeutics of neurodegenerative diseases
 
13:05

IMGT/HighV-QUEST for NGS scFV analysis from antibody combinatorial libraries

  • Next generation sequencing (NGS) has recently emerged as a new method for the characterization of high throughput immunoglobulin (IG) or antibody immune repertoires both in vivo and in vitro
  • A double challenge remains for the NGS sequencing of scFv from combinatorial libraries: firstly, the scFv length is > 800 bp, and secondly, there is no tool for the analysis of two V domains in a single chain
  • Using IMGT/HighV-QUEST with the novel functionality for scFv allowed the analysis and characterization of the association of the VH and VL in ~450,000  NGS scFv PacBio reads of ~1000 bp from a selected combinatorial library
 
13:05

Insights from native mass spectrometry and ion-mobility mass spectrometry for antibody and antibody-based product characterization

  • Native MS and its hyphenation to size exclusion chromatography for mAbs analysis
  • Ion-mobility MS for conformational characterization
  • Intact mAb analysis
 

13:25 Networking Lunch

Looking towards the future

Chaired by Alain Beck, Senior Director, NBEs Analytical Chemistry, Pierre Fabre, Associate Editor, mAbs

Eric A Hughes
14:25

Future directions: oral delivery of biologics

  • State of biologics market today and the quest to transform injectables into pills
  • Historical challenges of delivering biologics orally
  • New advances in oral delivery:  spotlight on Rani Therapeutics
    • Introduction to Rani’s innovative oral delivery platform
    • Rani’s progress to date
    • PK data (Rani vs. subcutaneous injections) 
  • What the future holds:  the impact oral delivery would have on the biologics market
 
Dr Ulrich Brinkmann
14:45

Next generation bispecific antibodies

  • Bispecific Antibodies: from early concepts to drugs
  • 20 years (Coloma & Morrison 1997) of recombinant bsAb concepts - why did it take so long?
  • Diversity of formats - must have or nice to have?
  • BsAb drugs and bsAbs in clinical development
  • What comes next?
 
Dr Andreas Hougaard Laustsen
15:05

Novel snakebite antivenoms based on oligoclonal recombinant antibodies

  • Snakebite - the world’s most neglected tropical disease
  • The use of toxicovenomics (functional venom proteomics) to identify medically relevant snake venom toxins
  • The use of phage display for discovery of human antibodies capable of neutralizing snake toxins
  • Manufacturing perspectives for recombinant antivenoms
 
Dr Janice Reichert
15:25

Antibodies to watch in 2018

  • A new record (14) for recombinant antibody products granted first marketing approvals may be set in 2017. These products, and those that might be granted approvals in 2018, will be identified.  
  • Antibody therapeutics in Phase 3 clinical studies will be discussed, and those likely to move to regulatory review in 2018 will be noted. 
  • New data on antibody therapeutics development metrics, including clinical phase transition and approval success rates, will be presented.
 
15:55

Closing remarks from Terrapinn

16:00 End of Congress

 
 
last published: 19/Oct/17 09:05 GMT