2017 Archived Content

Optimisation & Developability Track Banner

With the myriad of new therapeutic concepts and formats, it is imperative for companies to come up with the best and fastest way to assess the molecule’s developability; optimise the molecule’s properties for half-life extension, solubility and stability; and engineer them to improve affinity, specificity and efficacy while reducing aggregation. These early-stage screening and optimisation strategies not only contribute to streamlining efficacy-toxicology evaluation, but also allow for pharmacologically effective, and developable candidates to reach the clinic and eventually the patients, faster. CHI’s 8th annual Optimisation & Developability conference invites scientists with proven technologies and creative approaches to share their strategies in evaluating and optimising the best candidate to move forward.

Final Agenda

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SC5: The Multi-Attribute Method (MAM) for Improving Product and Process Development

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12:00 Registration


13:40 Welcome from PEGS Europe Team

Christina C. Lingham, Team Lead, PEGS Europe

13:45 Moderator’s Opening Remarks

Marie Kosco-Vilbois, Ph.D., CSO, NovImmune SA

13:50 Safety Considerations for Development of Immune Agonist and Immune Antagonist Biotherapeutics

Rakesh_DixitRakesh Dixit, Ph.D., DABT, Vice President, Research & Development, and Global Head, Biologics Safety Assessment, MedImmune (A member of AstraZeneca Group)

In this keynote presentation, the challenges of biotherapeutics impacting on the immune response, and the challenges investigators face managing, dose, scheduling, and satisfying the regulatory requirements will be discussed. The checkpoint pathways modulation used for cancer immunotherapy has a natural role in controlling autoimmune diseases such as Type 1 Diabetes and Lupus. Immunotherapies in general, and technologies modifying T cell function and those involving cytokines present dangers of cytokine storm, autoimmune disease, cardiovascular disorders, and additional challenges, especially when used in combination. Strategies to manage and mitigate immune related safety events will be presented.

14:30 Learning What Works from Successful Tumour Infiltrating Lymphocyte Therapy

Andy_SewellAndrew Sewell, Ph.D., Professor, Division of Infection and Immunity, Cardiff University School of Medicine

Over 20% of melanoma patients that have been refractory to other treatments undergo complete lasting remission after adoptive cell transfer of tumor-infiltrating lymphocytes (TILs). Dissection of these extraordinary successes by examining the dominant tumor-reactive T-cell clonotypes in the TIL infusion product and patient blood after ‘cure’ has revealed some surprising, exciting new HLA-restricted and non-HLA restricted targets that are expressed by many other tumour types.

15:10 Widening the Therapeutic Index: The Next Generation of Antibody-Drug Conjugates (ADCs)

John_LambertJohn M. Lambert, Ph.D., Executive Vice President Emeritus and Distinguished Research Fellow, ImmunoGen, Inc.

ADCs with potent tubulin-acting and DNA-acting agents can be effective anti-cancer agents with good TI. However, not all cell-surface targets have proven susceptible to the development of effective ADCs utilizing the first-generation ADC chemistries. Each element in the ADC design, the antibody, the payload, and the linker (both site of attachment on antibody and payload-release mechanism) are important considerations. Application of the growing “ADC Toolbox” to current and future ADC developments will be discussed.

15:50 Refreshment Break in the Exhibit Hall with Poster Viewing


16:50 Chairperson’s Remarks

Lars Linden, Ph.D., Head, Protein Biochemistry, Biologics Research, Cell and Protein Science, Bayer AG

16:55 Developability Risk Assessments to Select Preclinical Antibody Candidates

Dorina_SaroDorina Saro, Ph.D., Senior Scientist, Cell and Developability Sciences, Janssen R&D, Pharmaceutical Development and Manufacturing Sciences

An overview of the developability assessment of preclinical candidates at Janssen will be given at the presentation. Specific case studies with a focus of the assessment of bispecific candidates will be included.

17:25 Predictive Assays for Pharmacokinetics to Guide Lead Selection and Engineering

Hubert_KettenbergerHubert Kettenberger, Ph.D., Senior Principal Scientist, Large Molecule Research, Roche Innovation Center Munich

For most biotherapeutics, long in vivo half-live and thus long durability is desired. Comparing many different monoclonal antibodies, we and several other authors observed large differences in their pharmacokinetics which cannot be explained by different Fc:FcRn interactions alone. Unspecific, low-affinity interactions with highly abundant targets may, however, negatively impact PK. We present predictive assays to identify mAbs with fast clearance during the lead selection and protein engineering phase.

17:55 Epitope Binning Studies May Reveal Displacement in mAb Libraries

Alex_van-der-KooiAlex van der Kooi, Manager, Interaction Laboratory, IBIS Technologies

Array-based SPR-imaging devices (MX96 SPR imager, IBIS Technologies) are ideally suited for epitope binning experiments with large panels. Within these large panels, antibodies may be identified that target closely adjacent or minimally overlapping epitopes. These mAbs can displace one another. Data is presented illustrating the displacement process.

18:10 QPix Select HT – Seamless Integration into Larger Automation Workstations

Dagmar_ZunnerDagmar Zunner, Ph.D., Field Application Scientist, BioProduction Development, Molecular Devices

The QPix™ 400 series colony pickers offer the unique option to simultaneously detect colonies and quantify fluorescent markers in a pre-screening step before picking. The QPix Select HT System integrates seamlessly into larger automation workstations. It can be incorporated into an existing automated system, or delivered automation-ready for future integration.

18:25 Welcome Reception in the Exhibit Hall with Poster Viewing

19:25 End of Day


07:45 Registration and Morning Coffee


08:30 Chairperson’s Remarks

Chris Lloyd, Senior Scientist, Protein Engineering, Antibody Discovery and Protein Engineering (ADPE), MedImmune

08:35 Fc Engineering for Improved Developability and Retained Biological Activity

Martin_Jack_BorrokM. Jack Borrok, Ph.D., Scientist II, Antibody Discovery and Protein Engineering, MedImmune (AstraZeneca)

Modifications of the IgG Fc have allowed for serum persistence and immune engagement to become tunable properties for therapeutic monoclonal antibodies and Fc fusion proteins. These mutation combinations however are rarely “plug-and-play” and can introduce developability problems not present in the parental antibody. This talk will focus on strategies to assess the stability of Fc mutants and outline our engineering approach to improve the developability of antibodies containing Fc mutations while retaining tailored biological activity.

09:05 Rational Design of an Fc-Fusion Therapeutic with Optimal Drug-Like Properties

William_SomersWilliam Somers, Ph.D., Vice President, Biomedicines Design, Pfizer, Inc.

Fusion of endogenous proteins with an antibody Fc region has successfully led to dramatic improvements in pharmacokinetics. Unfortunately, these will often have poor drug-like properties that limit their utility and increase risk of failure. These challenges include production cell culture clipping, complex purification schemes, unusual formulations, and in vivo aggregation/stability. We will present a systematic process to discover therapeutic leads with dramatically improved properties along with case studies.

09:35 Developability: Looking for “Drug-Like Properties” Right from the Start of Antibody Lead Discovery

Lars_LindenLars Linden, Ph.D., Head, Protein Biochemistry, Biologics Research, Cell and Protein Science, Bayer AG

  • How to address developability early on in lead discovery
  • Towards in silico and higher throughput in vitro methods
  • Developability in LO Phase and how to extend an antibody platform to non-platform molecules
  • Specialties for Antibody-drug conjugates or targeted Thorium Conjugates (Radiotherapy)

10:05 Integration of Developability Assessment and Protein Engineering for Optimization of Therapeutic Antibodies

Chetan_PatelChetan Patel, Ph.D., Principal Research Scientist, Biotherapeutics Discovery Research, Eli Lilly & Company

This presentation will discuss the analytical characterization of developability attributes of therapeutic molecules during discovery and provide case studies of engineering strategies to mitigate developability risks.

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


11:15 KEYNOTE PRESENTATION: Developability Assessment of Biologics – A Concept for Early Lead Selection 

Thorsten_LorenzThorsten Lorenz, Ph.D., Global Head, Developability Assessment, Integrated Biologics Profiling, Novartis Pharma AG

Early lead selection of biotherapeutics during preclinical development requires careful characterization of a variety of molecule properties to reduce the risk for encountering unexpected obstacles during technical development. The developability assessment concept applied at Novartis combines information about expression, aggregation propensity, process fit, stability, solubility, physicochemical properties, in vivo fitness and immunogenicity of potential candidates. The presentation will provide an overview about the concept and highlight the success with selected examples.

11:45 Developability Assessment for Bispecific Antibodies

Sagit_HindiSagit Hindi-Jacoel, Ph.D., Research Advisor, Biologics Technology, Eli Lilly and Company

Bispecific antibodies offer dual epitope targeting with the potential for enhanced therapeutic benefit. However, their development can present unique challenges due to their unnatural assembly. The development and optimization of BsABs requires a comprehensive assessment of their critical quality attributes at an early stage of discovery and relies heavily on bioanalytical characterization. This presentation will discuss our integrated bioanalytical strategy to enable an efficient developability assessment of IgG-like bispecific antibodies.

12:15 Improving Protein Validation and Characterization Workflows with Faster Sample Quality Analysis

Dennis_BreitsprecherDennis Breitsprecher, Ph.D., Product Manager, Product Development, NanoTemper Technologies GmbH

12:30 Computational Approaches for Assessing Developability and Optimization of Biotherapeutics

Nels_ThorsteinsonNels Thorsteinson, Scientific Services Manager, Biologics, Chemical Computing Group, Inc.

Protein surface hydrophobic patches can lead to aggregation, poor solubility, and cross-reactivity. We present methods where homology models of sets of antibodies and related biologics with their calculated hydrophobic patches and charge properties may be used to perform solubility predictions. Liability reduction and solubility optimization while maintaining affinity are discussed.

12:45 Luncheon Presentation: Optimizing Drug Dosing by PK Modulation - The Potential of Veltis® Engineered Albumins

Nicholas_Joseph_MartinNicholas Joseph Martin, Ph.D., Research Scientist Bioprocess Characterisation, Albumedix

Albumin has been used for decades to enhance the pharmacokinetic and pharmacodynamic properties of drug candidates. We will describe rationally engineered albumins that further enhance these properties; variants with modified affinity to FcRn offer more than double the half-life extension to a drug candidate compared to that achieved with native albumin. We also present new engineered albumin variants with additional free thiol groups that allow multi-valent site specific drug loading.

13:15 Session Break

13:30 Dessert Break in the Exhibit Hall with Poster Viewing


14:00 Chairperson’s Remarks

William Somers, Ph.D., Vice President, Biomedicines Design, Pfizer, Inc.

14:05 Engineering the Surface Properties of Antibodies to Reduce Self-Association and Aggregation

Chris_LloydChris Lloyd, Senior Scientist, Protein Engineering, Antibody Discovery and Protein Engineering (ADPE), MedImmune

Undesirable physicochemical properties, such as aggregation and chemical degradation, may preclude the development of therapeutic antibodies, due to potential issues during manufacturing, storage and in vivo administration. Avoiding such properties early on in drug discovery is therefore desirable. My presentation will highlight practical screening and antibody engineering strategies that are effective in identifying lead candidates suitable for development as a drug.

14:35 Rational Optimization of Peptide Aggregation by in silico Modeling and Efficient Experimental Profiling

Andreas_EversAndreas Evers, Ph.D., Senior Scientist, Structure, Design & Informatics, Integrated Drug Discovery, Sanofi

Orthogonal experimental methods and different in silico approaches are continuously applied in an iterative manner for the prediction of aggregation tendency, considering requirements of the final formulation, such as compatibility with phenolic preservatives and the targeted pH range. The presentation includes an example demonstrating how aggregation events were correlated with structural features and the learnings were prospectively translated into the design of new molecules that do not exhibit aggregation tendency.

15:05 Structural Versatility of CDR-H3 as a Risk Factor

Hiroki_ShiraiHiroki Shirai, Ph.D., Executive Fellow, Modality Research Laboratories, Astellas Pharma Co., Ltd.

Analysis of antibody CDR-H3 structures by simulation and informatics approaches enabled us to set up high resolution antibody modeling, and eventually identify “design-able” antibodies which are relatively easy for model building and engineering. Designability is related to CDR-H3 versatility, and the choice of undesignable antibody would waste time/cost for antibody optimization.

15:35 The Affimer® Scaffold: a Flexible Platform for the Generation of Affinity Reagents

Geoff_PlattGeoff Platt, Ph.D., Senior Applications Scientist, Avacta Life Sciences

Affimer proteins are next-generation affinity scaffolds with multiple properties that make them amenable as a platform for immunoassay and biotherapeutics development. Benefits include speed to discovery, ease of production, batch-to-batch reproducibility, specificity and stability. Using phage display, Affimer binders have been identified to a wide range of targets (including ZikaNS1, Toxin B, Trastuzumab and PD-L1) XelPleX is used as a label-free screening system to assess Affimer binding to a target of interest.

16:05 Refreshment Break in the Exhibit Hall with Poster Viewing

16:45 Highly Efficacious Effector Function Attenuating Mutations that Maintain Antibody Stability and Reduce Toxicity in Mice

Travis_BainbridgeTravis W. Bainbridge, MSc, Senior Scientific Researcher, Protein Chemistry, Genentech, Inc.

We demonstrate that commonly used effector function variants that are efficacious in attenuating cytotoxicity in primates, retain potent complement activation capacity in mice. We describe a novel combination of variants that eliminates complement binding, fixation and Fcγ-dependent ADCC in both murine IgG2a and human IgG1, unlike aglycosylated antibodies. We further demonstrate that human and murine antibodies containing these variants have typical pharmacokinetics in rodents and retain thermostability.

17:15 Advancing the Discovery and Development of Immunotherapeutics with Large, Multiplexed Experiments on Suspension Cells

Mark_CarterMark Carter, New Mexico Senior Assay Consulting Scientist, IntelliCyt, A Sartorius Company

Benjamin_TyrrellBenjamin Tyrrell, TS Scientist, Sartorius Stedim, BioOutsource Limited

Exciting advances are being made in novel immunotherapies for treatment of cancer and other diseases. The discovery and development of these therapies requires new tools that can evaluate their effect on cells and proteins of the immune. This presentation will highlight how the iQue Screener PLUS platform is being used to discover new antibodies, to understand functional efficacy of immunotherapies, and to screen for highly productive clones during the cell line generation process.

17:45 Optimization of Biologics Using mRNA Display and NGS

Julie_SuLinhui Julie Su, Ph.D., Senior Research Investigator II, Molecular Discovery Technologies, Bristol-Myers Squibb

In this talk, I will describe library design, selection strategies, and data analysis using next-generation sequencing (NGS) for discovery of biologic leads.

18:15 End of Optimisation & Developability