European Antibody Congress - Agenda Day 2


European Antibody Congress 2018, Day 2

08:00 Registration Opens

08:50 Conference doors open

Keynote: Combination therapies

10:10 Networking refreshment break

Targeting and specificity

Bispecific discovery

Armed antibody development - Pre-clinical development

CMC and Developability

Chaired by TBC

Chaired by John Delaney, Executive Director, Amgen Biologics Discovery

Chaired by Stuart Hicks, Associate Director of Pipeline Research & Development, ImmunoGen

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

Antibodies - Protein Engineering

Changes in complementarity-determining regions significantly alter IgG binding to the neonatal Fc receptor (FcRn) and pharmacokinetics

  • Examined the role of IgG domains distal from the Fc in altering the affinity between IgG and FcRn
  • Identified that variable domains, and in particular complementarity-determining regions (CDRs), significantly alter binding affinity to FcRn in vitro and determined that affinity values correlated with calculated isoelectric point values
  • Demonstrated that tighter affinity values of IgG molecules to FcRn trend with faster in vivo clearance of a set of IgG molecules differing only by 1-3 mutations in human FcRn transgenic mice
Antibodies - Bispecifics

Antibody discovery considerations for ImmunoOncology bi-specific molecules

  • Antibody Discovery
  • T-cell Engager modalities
  • Bi-Specific scaffolds
Antibodies - Armed Antibodies

Pre-clinical development of HuMax-AXL-ADC

  • Axl as a therapeutic target in human cancers
  • HuMax-AXL-ADC antibody generation and mechanism of action
  • Efficacy data for HuMax-AXL-ADC in preclinical models
Antibodies - CMC and Developability

Cutting edge analytical and multiple attributes methods for mAbs and ADCs

  • 2 to 4D - LC-MS profiling and structure assessment
  • Insights gained from native, Ion Mobility, HILIC and CE mass spectrometry
  • Forced degradation, developability and comparability workflows
Antibodies - Protein Engineering

The importance of antibody isotype and Fc receptor interactions in engineering cancer immunotherapies

  • Immunomodulatory mAb can employ multiple mechanisms in tumours
  • Potential mechanisms depend on mAb isotype and FcγR availability
  • mAb engineering can allow multiple mechanisms to be engaged to therapeutic effect
Antibodies - Bispecifics

Multispecific CODV-Ig derived protein therapeutics – examples and future perspective

  • Overcome limitations of existing bispecific bio therapeutics we created the universally applicable CODV (Cross -Over Dual Variable)–Ig format
  • Serves as a versatile platform for the development of bi- and multi-specific protein therapeutics
  • Will highlight the flexibility and variability of the corresponding technology
  • Show how this can be applied to different biological questions in different case studies and outline how a new high throughput biologics system will be used to further improve the therapeutic properties
Antibodies - Armed Antibodies

Expanding the potential of ADCs: EpCAM-targeting Probody Drug Conjugates

  • Creating ADCs that are selectively activated in the tumor microenvironment would allow the inclusion of targets that would otherwise be incompatible with traditional ADC development due to high normal tissue expression
  • By combining ImmunoGen’s linker-payload technologies with CytomX’s ProbodyTM technology, we have generated Probody drug conjugates designed to preferentially bind EpCAM expressed in tumors and not in healthy tissues.
  • We will describe the preclinical activity and safety of EpCAM-targeting Probody drug conjugates
Antibodies - CMC and Developability

Accelerating the timeline to GMP

  • Accelerated FIH Development requires knowledge of mAbs, bispecifics, fc-fusion proteins, recombinant enzymes, and other glycoproteins, and a good understanding of process and analytical tools to drive development from cell line development through manufacturing is critical.
  • KBI will be providing a roadmap to accelerated FIH Development and also an overview of KBI’s vast capabilities to support development and manufacturing of biomolecules
Antibodies - Protein Engineering

Biophysical characterization of bispecific antibodies for enhancement of dual-targeting specificity

The measurement of binding rates and avidity effects in the simultaneous engagement of two antigens by a bispecific antibody is key for optimizing target specificity early in the development process. I will describe the utilization of the switchSENSE® biosensor to emulate the display of two different target antigens on a cancer cell surface. Precise control of the relative abundance and spatial arrangement of two antigen species on the sensor is achieved using DNA-guided surface functionalization and dual-color fluorescence detection. The quantitative analysis provides insight on how to adjust the individual affinities of the bispecific antibody arms, so that most favorable conjoint action is achieved, i.e., maximal on-target and minimal off-target binding, respectively.
Antibodies - Bispecifics

Next generation bispecific antibodies

  • Platform technology vs format zoo: how to keep the right balance
  • Format defines function: size, valency, geometry, flexibility
  • Format examples in clinical development
  • Novel formats with differentiated features
Antibodies - Armed Antibodies

Click chemistry-triggered drug release from tumor-bound ADCs

  • Learn how non-internalizing receptors can become amendable to ADC therapy
  • Development of a diabody-based MMAE ADC against non-internalizing TAG72 with a high tumor uptake and low retention in healthy tissues
  • ADC tumor binding and blood clearance is followed by systemic administration of a chemical activator that cleaves the ADC linker, leading to potent antitumor activity in murine tumor models
  • In contrast, the analogous ADC comprising a protease-cleavable linker is not effective in these tumor models
Antibodies - CMC and Developability

Establishing highly precise, low material consuming biophysical platform for biologics developability assessment

  • New biophysical applications for Biologics characterization using
    • Second Harmonic Generation (SHG)
    • Nano Digferential Scanning Fluorimetry (nano-DSF)
    • Microscale Thermophoresis (MST)
  • Kinetics for thermal stability and Activation energy barrier determination for Biologics stability assessment
  • Long-terms stability prediction by computational biophysical approaches

New formats and developability

Chaired by TBC

Antibodies - Protein Engineering

Creating multifunctional VH-based biologics using Humabodies from the Crescendo Mouse

  • Proprietary transgenic mouse generates highly diverse fully human VH domain (‘Humabody’) building blocks
  • Fully modular plug & play approach lacks the constraints of traditional mAbs and enables a radical rethink of how a multifunctional molecule can be designed and assembled to deliver enhanced therapeutic benefit.
  • Examples of differentiated biology will focus on applications in immuno-oncology and Humabody drug conjugates
Antibodies - Bispecifics

Application of the novel heterodimerization plattform Fc1k in mono- and multispecific molecules

  • Principles of the novel heterodimerization strategy
  • Generation of a lead candidate as platform module
  • Examples for bispecific applications
  • Future opportunities
Antibodies - Armed Antibodies

Functional disulfide re-bridging enables native full antibody DAR 2, 4 & 8 formation, site-selective orthogonal dual modification and homogeneous fragment drug conjugates

  • Site-selective modification of antibodies (including robust serum stability, in vitro selectivity, in vivo efficacy with options for DAR 2, 4 & 8, dual drug conjugates and fragment drug conjugates).
  • Use of chemical linkers to form bi- and tri-specific scaffolds 3. Application of technology to generate oriented antibody fragments on nanoparticle surfaces
Antibodies - CMC and Developability

Globally-optimised clinical candidates for maximised development success

  • Many therapeutic antibody candidates carry unnecessary amino-acid content in their binding domains
  • This extraneous content leads to significant proven CMC and clinical development risks
  • This presentation will present novel data translating fundamental antibody biology insights into improved-quality product candidates
Antibodies - Protein Engineering

Engineering aggregation resistant human domain antibodies

  • Two novel highly diverse synthetic human domain antibody libraries
  • Versatility in targeting difficult epitopes
  • Strategies to engineer aggregation resistance
Antibodies - Armed Antibodies

Extended Q&A

Your chance to ask the speakers questions!
Antibodies - CMC and Developability

Clinical development of patient-centric injectable biologics-device combination products

  • The development of drug-device combination (DDC) products is a strategic imperative across the biopharmaceutical industry for injectable biologics
  • A successful clinical strategy to address changes in manufacturing processes for drug substance as well as for DDC presentations needs to be risk-based and scientifically sound
  • An injectable DDC needs to be user-centric, and usability assessment in real-world clinical settings may be required to support the approval of a DDC

13:05 Networking Lunch

Protein engineering New formats and developability

Bispecific discovery

Armed antibody development – clinical development


Chaired by TBC

Chaired by John Delaney, Executive Director, Amgen Biologics Discovery

Chaired by Stuart Hicks, Associate Director of Pipeline Research & Development, ImmunoGen

Chaired by Patrick Garidel, Head of Process, Purification and Pharma Development, Boehringer Ingelheim

Antibodies - Protein Engineering

Genetic encoding of a cyclopropene for the rapid and efficient generation of stable antibody conjugates

  • Efficient transient and stable expression systems
  • Rapid conjugation of tetrazine-bearing molecules
  • Dihydropyridazine bond stability in serum
  • Generation of a potent and selective ADC
Antibodies - Bispecifics

Bi/Multi-specific antibodies- technologies development

  • Generation of multi-specific antibodies will be discussed
  • A new solution to avoid HC/LC mispairing and a fast screening method to visualize and deselect mis-paired antibodies will be presented
Antibodies - Armed Antibodies

Novel immune-stimmulatory ADCs (iADCs) for effective targeting of solid tumors

  • Site-specific conjugates with ultra-potent anthracycline toxins
  • Immune-oncology function of NBE’s iADCs
  • Preclinical validation of a ROR1 targeting iADC
Antibodies - CMC and Developability

CMC aspects of highly concentrated protein formulations

  • Why do we need HCLF?
  • How high is high?
  • CMC challenges
  • Some related case studies
Antibodies - Protein Engineering

Antibody protein sequencing with mass spectrometry

  • Robust service to routinely sequence antibodies proteins directly
  • Accurate determination of Isoleucine and Leucine using mass spectrometry
  • Beyond 100% protein coverage by examine individual amino acid
Antibodies - Bispecifics

Mechanistic modelling and simulation for bispecific antibodies and beyond

  • Bispecific target space: in solution vs cell membrane-bound
  • Bispecific cross-linking on cell membrane targets
  • Implications for biparatopics and cell-cell cross-linking antibodies
  • Pharmacokinetics of bispecific antibody constructs
Antibodies - Armed Antibodies

Improving single-cell delivery of antibody and protein-drug conjugates: Multiple strategies to increase drug distribution and efficacy

  • The distribution of cytotoxic payloads from antibody drug conjugates within a tumor, not just the total amount of payload, has a significant impact on efficacy
  • Multiple strategies can improve tumoral distribution including target selection, protein structure, and dosing to increase efficacy
  • These approaches and relevant examples will be discussed in the context of when each strategy is appropriate
Antibodies - CMC and Developability

Advantages of perfusion processes for the production of difficult to express proteins

  • What are the currently used perfusion systems?
  • Advantages and challenges of perfusion strategies
  • Case studies
Antibodies - Protein Engineering

Fighting pathogens and toxins with human and human-like antibodies

  • Recombinant antibodies for biodefense
  • Neutralizing and protective antibodies against viruses (Marburg virus, VEEV and WEEV)
  • Neutralizing and protective antibodies against toxins (botulinum toxins, diphtheria toxin)
  • Germline humanization of macaque antibodies
Antibodies - Bispecifics

CD47 targeting bispecific antibodies

  • Rationale for CD47 neutralization in cancer
  • Targeting CD47 with bispecific vs monoclonal antibodies – what’s the difference?
  • Blockade of CD47 with bispecific antibodies promotes tumour elimination in vivo and modifies the tumour microenvironment
Antibodies - Armed Antibodies

Chemoselectively induced bioconjugation for stable and homogeneous ADCs

  • Linkage technology for both: native (cysteine) and engineered antibodies (chemo-enzymatic) has been developed in our laboratory
  • Chemically induced phosphonamidate electrophiles for selective conjugation to Cys-residues
  • Conjugates are stable in human serum and efficient in vivo
  • Intracellular lability opens the way to a novel, inherent drug release technology
Antibodies - CMC and Developability

Enabling drug development of therapeutic proteins at the interface of research to development

  • Developability assessment of therapeutic proteins
  • State-of-the art cell line and strain development
  • A toolbox concept enabling drug development of therapeutic proteins of a rich portfolio with increasingly complex molecule formats
Antibodies - Protein Engineering

Harnessing biotechnology against snakebite and other neglected tropical diseases

  • Snake venoms - a diverse arsenal of highly potent protein-based toxins
  • Cocktails of monoclonal human IgG antibodies with in vivo efficacy against snake venoms
  • Discovery of neurotoxin-targeting human IgGs using phage display technology
  • Using snake venom toxins to target parasitic diseases
Antibodies - Bispecifics

Extended Q&A

An opportunity to ask the speakers your questions!
Antibodies - Armed Antibodies

Radionuclide therapy using peptide nucleic acid (PNA)-mediated pretargeting of HER2-expressing tumors

  • We have developed a system for peptide nucleic acid (PNA)-based pretargeting of tumors, which can be used to overcome the problem with renal accumulation of HER2-binding affibody molecules
  • Experimental therapy with a HER2-binding affibody and 177Lu-labeled PNA probes show promising results in a mouse model: prolonged survival for treated mice and no observed toxicity
  • PNA-based pretargeting in combination with the HER2-targeting antibody trastuzumab resulted in clear visualization of HER2-expressing xenografts in mice
Antibodies - CMC and Developability

Analytical methods used to monitor size variants in new biotherapeutic modalities

  • Applications of SEC for bispecific mAbs
  • Complimentary CE-SDS for bispecific mAbs and single chain variable fragments

15:55 Networking Break

Pharmacokinetics and the therapeutic window

Chaired by Olivier Heudi, Senior Investigator I, Novartis Pharma

Christoph Roesli

CMC strategies to influence pharmacokinetics

  • Mechanisms influencing the pharmacokinetics of antibodies
  • API-related critical quality attributes influencing pharmacokinetics
  • Considerations for antibodies with and without effector function
Frank Brennan

Safety testing of monoclonal antibodies: new targets, new molecules, new challenges

  • In silico review of target biology
  • Rationale mAb design/selection to avoid unwanted biological/immune effects
  • In vitro studies: pharmacology/immunosafety studies to characterise Fab and Fc effects, off-target binding and immunogenicity
  • In vivo studies: safety/efficacy/PD studies in normal/disease models
  • Using safety, PK/PD and M&S data to select safe human starting doses and escalation schemes
Kevin Bateman

Direct quantitation of therapeutic sntibodies for pharmacokinetic studies using immuno-purification and intact mass analysis

  • PK of mAbs has traditionally been measured using ligand binding assays
  • The use of mass spectrometry can complement LBA results
  • Results comparing LC-MS with LBA will be presented from GLP studies
Rita Martello

Validation of a LC-MS/MS assay for the quantitation of a new trispecific antibody against AIDS virus HIV-1

  • A new trispecific antibody exhibits higher potency and confers complete immunity against a mixture of SHIVs in non-human primates
  • Toxicokinetic assessments required a GLP validate assay
  • Ligand-binding assays have been standard methods for measuring therapeutic antibodies, however not always suitable. In alternative, we developed and validated a fast and accurate LC-MS/MS assay for quantitation of the trivalent antibody in the toxicological studies

18:20 Poster presentation and networking drinks reception

last published: 28/Oct/18 15:15 GMT


There are two parts to the Festival of Biologics: the five world-class international conferences covering Antibodies, Immunotherapy, BioSimilars, Clinical Trials, and High Potency APIs; and an exhibition featuring the most exciting technology and solutions for pharma and biotech. There is a registration fee to attend the conferences. To visit the exhibition is free.


Conference 29 - 31 October • Exhibition & Seminars 29 - 31 October

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