EAC 2017 Day 2, Wednesday 1st November 2017

08:00 Registration Opens

08:50 Conference doors open

Strategies for oncology

Panel discussion

10:25 Networking Break

Discovery – Armed antibodies Target discovery and biomarkers

Develop – Bispecifics Preclinical development

Platform technology showcase

Chaired by Andrea Gonzalez-Munoz, Research Associate, MedImmune

Chaired by Ezio Bonvini, SVP & CSO, Research, Macrogenics

Chaired by Ulf Grawunder, CEO, NBE Therapeutics


Small is beautiful – Humabodies Drug Conjugates, HDC’s a real alternative to ADC’s

  • Crescendo is developing a pipeline of novel multifunctional Humabody® therapeutics demonstrating excitingly differentiated efficacy compared with clinical mAbs
  • Optimally configured Humabody Drug Conjugates (HDCs) engage therapeutically valuable targets in a way that is different from whole antibodies, unlocking superior therapeutic index
  • Highly potent HDCs will play an important role in the next generation of targeted oncology therapeutics as a critical component of increasingly effective combination regimes

Engineering an Affibody® fusion protein trap towards therapeutic blocking of IL-17 in man

  • Psoriasis is an IL-17 driven disease.
  • An Affibody® based 18.6 kDa ligand trap was engineered to block IL-17A with femtomolar affinity
  • The trivalent bispecific fusion protein blocks IL-17 with unparalleled affinity and displays long plasma half-life as shown in man
  • Early development and data from Phase I/II will be presented

A better way to characterize monoclonal antibodies with Prometheus

  • Understanding the biophysical properties of monoclonal antibodies can provide powerful insights into screening and characterizing this important class of biologics.
  • Nanotemper-Technologies’ Prometheus platform which performs nano-Differential Scanning Fluorimetry (nanoDSF), a method that provides flexible analysis and ultra-high resolution of protein stability and aggregation will be discussed
  • Utilization of thermal and chemical unfolding as well as aggregation data on monoclonal antibodies can be used as predictive indicators in formulation and stability studies, ultimately resulting in improved biotherapeutic products.

A novel antibody drug conjugate targeting the Trypanosoma brucei haptoglobin-haemoglobin receptor to treat sleeping sickness

  • Taking advantage of receptor-mediated nutrient uptake by trypanosomes, toxin-conjugated monoclonal antibodies recognising these receptors could be used to target and deliver a toxin to the parasite The T. b. brucei haptoglobin-haemoglobin receptor
  • Monoclonal antibodies generated against the HpHbR N-terminal were conjugated to Pyrrolobenzodiazepine (PBD) toxins leading to targeted cell killing of trypanosomes at picomolar concentrations

Accelerating the development of protein therapeutics using advanced cell engineering

  • Large-scale transient expression of quality antibodies, bispecifics and Fc fragements
  • Rapid generation of high-yield stable pools and clones
  • Genome modification for improved yield and fine tuning of post-translational modifications

Exceptional human antibody discovery with a best-in-class transgenic mouse

  • Examine a unique transgenic platform: expression of a complete human antibody variable domain repertoire drive by optimized murine genetic sequence – The Trianni Mouse.
  • Review licensee case studies and internal validation data
  • Learn about future strains and modifications under development

Develop – Bispecifics Clinical Development


A smart microfluidic technology for early discovery and analytics

  • A new “intelligent” LabChip microfluidic platform for high throughput quantitation and quality screening of protein products
  • Intelligent System Technology method utilizes a microchip which utilizes real-time electro-hydrodynamic optimization to eliminate variability in reported results
  • Using the Labchip system one can attain high reproducibility of samples, greater accuracy and sensitivity. The intelligent microfluidic platform is designed to address future of protein product development and downstream production processes in biopharmaceutical industry

Reserved for CMC Biologics


High quality antibodies for therapeutic applications

  • Immunized-mass humanized antibody libraries
  • Yeast display of full length IgG and bispecific antibodies
  • Functional antibodies against challenging targets
  • Optimal developability

Novel DART and TRIDENT molecules with unique modes of action

  • Advancing half-life extended DART molecules for redirected T-cell killing
  • Strategies to target checkpoint and costimulatory pathways
  • Adapting TRIDENT protein’s avidity and valency to address diverse modes of action

Advancing DART molecules in the clinic

  • Translating pre-clinical information in the clinic
  • Early clinical pharmacodynamic
  • Preliminary clinical experience

Bioanalytical PK support for immunotherapeutics: the need for sensitivity combined with broad assay range – case studies

  • Ultra sensitive GLP/GCP regulated immunoassay sample testing support for immunotherapeutics and other large-molecule Biologics
  • The need for assay sensitivity in combination with continuous quantification range in PK sample testing support for antibody-based drugs is discussed
  • Additional ligand-binding assay (LBA) solutions to typical challenges in PK support for large-molecule drugs in general, e.g. sample volume restrictions, are discussed

Antibody therapeutics - pre-clinical development


Bstrongximab, a novel antibody-drug-conjugate targeting metastatic cancer

  • Embryonic antigens expressed in cancers but not normal tissues offer a new class of cancer targets for development of antibody-drug-conjugates
  • Bstrongximab is a human chimeric antibody-drug-conjugate with high affinity and specificity to a novel embryonic cancer target expressed in colon, gastric, pancreatic and esophageal cancers
  • In vitro and in vivo preclinical data show Bstrongximab to be a highly specific and potent cancer antibody-drug-conjugate

Predicting and Managing Unwanted Immune Responses to Antibodies including utilisation of MHC-Associated Peptide Proteomics (MAPPs)

  • Accurate and sensitive ways to assess the potential immunogenicity and development of anti-drug antibodies against proteins and antibodies ex vivo by measuring CD4+ T cell responses
  • Methods for managing and reducing potential immunogenicity
  • Introducing MHC-Associated Peptide Proteomics (MAPPs) to augment data sets to better inform immunogenicity risk

ProTIA – Bispecific T cell engagers designed for local activation by tumor-associated proteas

  • ProTIA molecules utilize our proprietary XTEN™ protein polymer for half-life extension and to enable rapid microbial production as single protein chain
  • The XTENylated form of ProTIAs forms an inactive precursors with low systemic toxicity
  • XTEN is released at the tumor site by tumor associated proteases resulting in a 300-1000x gain in activity
  • ProTIA combines multiple mechanisms that contribute to the therapeutic index: A) Tumor antigen binding; B) Selective activation at the tumor site, C) The preferential accumulation of polymers in the tumor environment (EPR effect)

13:05 Networking Lunch

Chaired by John Delaney, Executive Director, Amgen Biologics Discovery

CMC and Developability

Chaired by Thomas Keating, Senior Director, Biochemistry, Immunogen

Chaired by Alexey Rak, Head of Bio Structure and Biophysics, Sanofi R&D


A sweet spot for antibody discovery

  • Opportunities for generating mAbs against sugar epitopes (anti-glycan mAbs)
  • Anti-glycan mAbs has increased specificity compared to anti-protein mAbs 
  • Mechanism of action as naked mAbs, ADC or ADCC against target cells

Bringing PBD-ADCs to the clinic

  • Introduction to PBDs
  • Preclinical data on ADCs targeting CD19, CD25, CD22 and HER2
  • Translation to the clinic : PBD PD biomarkers
  • Clinical validation: Current landscape of advanced PBD-ADCs
  • Clinical plans and current status of the ADC-Therapeutics pipeline

Integrating novel tools into development workflow of antibodies: nanoDSF and MST for discovery, development and QC

  • Biophysical approaches are routinely used to assess biologics activities, stability and quality
  • Modern drug discovery operations require characterization of biomolecular interactions to be both time- and cost-effective as well as to be highly precise and reproducible
  • Here we report applications of two novel methods nano-Diffrential Scanning Fluorimetry (nanoDSF ) and MicroScale Thermophoresis (MST) that we are applying in our biologics discovery and characterization operations
  • The examples of the demonstrated effectiveness of the nanoDSF and MST will be presented and discussed

Discovery – Bispecifics Early discovery and analytics

Develop – Armed Antibodies Preclinical development


Bi-Specific Antibodies: Discovery and Engineering

  • Strategies and challenges associated with bi-specific antibody discovery
  • Engineering strategies and formats for bi-specific antibodies
  • Challenges associated with production of bi-specific modalities

Biopharmaceutical R&D – partnered

  • Diverse licensing-based business model
  • Therapeutic antibody angles
  • OmniAb® technology
  • OmniAb® business

The Saturn mAb(TM) platform: efficient, high throughput monoclonal antibody production

  • Saturn Platform Mission: Offer competitive, de-risked, rapid and reliable mAb process implementation and manufacturing capacity that meets regulatory standards and client needs
  • Platform is built around disposable technology and standardised equipment, raw materials, and consumables, which increase efficiency and reduce cost, lead times, and risk
  • The pilot and manufacturing facilities are dedicated to Saturn programmes taking advantage of multiproduct ballrooms and process closure
  • Options: Saturn mAb Plus™, starting with Fujifilm's Apollo™ cell line, or Saturn mAb Transfer™, starting with a client cell line

Information content and molecular complexity: how important are the size and design of libraries?

  • Selections for HIV-1 entry inhibitors used a variety of libraries
  • We analyzed the winning sequences, to determine how the library design may have dictated their emergence
  • The role of library design and library size will be examined
  • Results may lead to a deeper understanding of how to set up successful selections

Preclinical validation of site-specifically conjugated ADCs with potent anthracycline payloads in solid and hematologic tumor models

  • Rationale of site-specifically conjugated ADCs
  • Validation of a novel ultrapotent anthracycline-toxin in ADCs
  • Preclinical validation of NBE’s lead ADCs in preclinical tumor models
  • Characterization of the immune-oncology function of NBE’s ADCs

The production of a novel scFv against coeliac disease – from gene to final product

  • Introduction to coeliac disease and a novel scFV for treatment
  • Overview of the scFV inclusion body process and challenges therewith
  • Integrated Bioprocessing – how does one Unit Operation influence the other in the scFV IB process?
  • Is the final product useful and competitive to available treatment?

Develop – Armed antibodies Clinical development


Accelerating the biotech value chain by implementation of the octet technology platform

  • Measurements of titer concentrations in a High throughput manner
  • Measurements of residual Protein A and residual CHO host cell proteins
  • Octet HTX platform technology

Payload considerations for IMGN632, a CD123-targeting ADC for acute myeloid leukemia

  • IMGN632 is a novel ADC linking an anti-CD123 antibody with ImmunoGen’s DGN549 payload via site-specific Cysmab technology
  • DGN549 is a DNA alkylator, as opposed to a DNA cross-linker
  • IMGN632 selectively kills AML cells over normal myeloid progenitors

The road to the clinic – a CDMO perspective

  • How early is early enough – considerations for cell line development
  • Titers vs. Critical Quality Attributes – are high titers really better?
  • Developability and the need to develop a robust process that will transfer into manufacturing
  • Analytics, Analytics, Analytics

15:55 Networking Break


Analysis of therapeutic molecules by high resolution and native mass spectrometry

  • Precise quantification of mixtures of bispecific IgG produced in single host cells by liquid chromatography-Orbitrap high-resolution mass spectrometry
  • Quantitative determination of protein-ligand affinity by online SEC high-resolution native mass spectrometry

An integrated approach to assess the developability of biologics

  • Developability assessment of Biologics: how to select the winners
  • Immunogenicity risk assessment
  • State-of-the art cell line development

Discovery – Bispecifics Target discovery and biomarkers


Targeted bispecific for progressive renal diseases

  • Improving therapeutic potential of renoprotective agents by increasing drug concentrations to target tissues and limiting systemic exposure
  • A case study using an acute model of fibrosis will be presented
  • Will discuss about identification and validation of new epitopes differentially expressed in diseased tissue for bispecific targeting approaches

Assessing mAb’s CMC related properties during early lead discovery stage by using endoplasmic reticulum as a physiological test tube

  • Depending on the properties embedded in the VL and VH regions, some mAbs show undesirable condensation propensity at high protein concentrations
  • Condensation-prone IgG mAbs can induce three different prominent cellular phenotypes during overexpression in mammalian cells
  • This talk will illustrate the predictive values of overexpression-induced cellular phenotypes in assessing the solution behaviors of individual mAb clones

Anti-cytokine therapies for inflammatory diseases

  • Selection of the most promising targets
  • Which approaches are likely to be successful and which not?    

CHOptimizer: Platform approach to fast and efficient titer and process improvement via CHO media optimization

  • A flexible and transparent media optimization service with the ambr® 15 microbioreactor system
  • Case study examples of improved fed-batch processes producing a variety of antibodies
  • An integrated platform approach driving improvement in peak viable cell density and titer adjusted to the individual manufacturing set-up

A novel heterodimerization strategy as plattform for mono- and multispecific drug candidates

  • Principles of the novel heterodimerization strategy
  • Generation of a lead candidate as platform module
  • Examples for further applications

Developability: looking for “drug like properties” right from the start

  • How to address developability early on in lead discovery 
  • In silico and higher throughput in vitro methods
  • Developability in LO Phase and specialties for ADCs

Chair's closing remarks


Chair's closing remarks


Chair's closing remarks

18:30 Poster Presentation and Networking Reception

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