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Developability assessment is not just a characterisation tool, but an enabling tool that can help companies find, develop and move the right molecules forward. It starts with designing the best screening parameters and techniques to predict the molecules’ developability and manufacturability, then coupling them with optimisation strategies to engineer and design the desired properties. If done right, it holds the promise to reduce cost and improve speed-to-market.

PEGS Europe’s 9th Annual Optimisation & Developability conference presents the proven strategies and creative approaches that scientists use to evaluate and optimize their best candidates to move forward.

Final Agenda

MONDAY 12 NOVEMBER | 09:00 - 12:00 | MORNING

Recommended Short Course*

SC4: Mutation and Selection Strategies beyond Affinity Optimisation - View Detailed Agenda

Brian Fennell, PhD, Senior Principal Scientist, BioMedicine Design (BMD), Pfizer Dublin

Fred Darmanin Sheehan, PhD, Senior Principal Scientist, Biomedicine Design, Pfizer Dublin

This course will begin with an introduction to the multiple display technology platforms, mutagenesis strategies and library generation options that exist to enable antibody optimization. In the simplest application, generated libraries can be selected for improved antigen binding. However, increasingly these strategies are being used for more complex applications from humanization to ortholog cross-reactivity, stability, solubility and specificity optimizations. This workshop will use case studies to help attendees navigate the complex workflows and technological options available to ensure success.

*Separate registration required.


12:00 Conference Registration (Foyer C)

Auditorium VI

13:30 Organizer’s Welcome

Mimi Langley, Senior Conference Director, Cambridge Healthtech Institute

13:35 Chairperson’s Opening Remarks

Lars Linden, PhD, Head, Protein Biochemistry, Biologics-Research, Cell and Protein Science, Bayer AG

13:45 New Insights into the Mechanistics of Antibody Pharmacokinetics

Kettenberger_HubertHubert Kettenberger, PhD, Senior Principal Scientist, Large Molecule Research, Roche Innovation Center Munich

Therapeutic antibodies with nearly identical Fc domains may show >10-fold differences in clearance. We systematically identified properties of the Fv domain that can cause atypical pharmacokinetic behavior. Using protein engineering, we created Fab mutants with defined biophysical properties and tested them in biochemical PK prediction assays and for in vivo clearance. Our results may pave the way for predicting and improving in vivo PK based on biophysical properties and biochemical assay data.


High Throughput Selection of Human Antibodies with Enhanced Developability Properties

Thomas Gallagher, Senior Bioinformatician, Kymab Ltd.

The successful development of biopharmaceutical drugs requires the timely identification, mitigation and resolution of the many challenges presented by the stringent requirements of biological activity, safety and physio-chemical properties. The Kymouse transgenic mouse platform, an advanced in vivo system for the rapid generation of fully human therapeutic monoclonal antibodies, has been coupled to a high throughput in silico developability assessment platform within Kymab. This platform enables the selection of developable high-quality drug candidates.

14:45 Multi-Parameter Ultra-High-Throughput Antibody Developability Screening by Mammalian Display

Dyson_MikeMike Dyson, PhD, CTO and Co-Founder, IONTAS Ltd.

Using directed integration of antibody genes by CRISPR/Cas9 or TALE nucleases, we have constructed large libraries of monoclonal stable cell lines. IgG-formatted antibodies are displayed on the cell surface permitting selection from the library of clones encoding desirable affinity, specificity, species cross-reactivity and “developability” properties. Two case studies will be presented where antibodies with well documented poor biophysical characteristics were modelled to identify surface hydrophobic and positive charge patches, and mammalian display used to select for antibodies with a superior developability profile.

15:15 Computational Approaches for Optimizing the Developability of Biotherapeutics

Nels Thorsteinson, Scientific Services Manager, Biologics, Chemical Computing Group

A candidate integrin α11-binding mAb was optimized for developability using molecular modeling and hydrophobic interaction chromatography (HIC). 97 variants of the residues primarily responsible for predicted hydrophobic regions were expressed and their HIC retention times measured. 3-dimensional protein property descriptors were used to train a QSPR model, producing improved correlation.  

15:45 Networking Refreshment Break (Foyer D)

Auditorium I

16:15 Moderator’s Opening Remarks

Janine Schuurman, PhD, Corporate Vice President, Research & Innovation, Genmab BV




16:20 Bicycles and Bicycle Drug Conjugates

Sir Gregory Winter, PhD, FRS, Master, Trinity College and Co-Founder and Director, Bicycle Therapeutics

Bicycles® are a novel therapeutic class of constrained bicyclic peptides that combine antibody-like affinity and selectivity with small molecule-like tissue penetration, tunable exposure and chemical synthesis. They have potential in many indications, including oncology, where Bicycles’ unique properties have been used to develop Bicycle Drug Conjugates® (BDCs); a novel toxin delivery platform which greatly improves toxin loading into tumour tissues. A BDC is expected to enter clinical trial in Q1 2018.

17:20 Paracrine Delivery: Therapeutic Biomolecules Produced in Situ

Andreas G. Plückthun, PhD, Professor and Director, Department of Biochemistry, University of Zürich

Cancer will have to be fought with cocktails of therapeutics acting locally, which may have to include therapeutic antibodies against receptors, checkpoint inhibitors, as well as cytokines to modify the tumor microenvironment. We have recently developed a technology of using non-replicative adenovirus carrying no viral genes, engineered to target desired cells and also to be shielded from the immune response, as a vehicle for simultaneous delivery of multiple genes of therapeutic proteins, produced and secreted by the infected cells.

18:20 Welcome Reception in the Exhibit Hall with Poster Viewing (Pavilion 1)

19:30 End of Day


07:45 Registration (Foyer C) and Morning Coffee (Foyer D)

Auditorium VI

08:30 Chairperson’s Remarks

Surjit Dixit, PhD, Vice President, Technology, Zymeworks, Inc.

08:35 KEYNOTE PRESENTATION: Developability Strategies to Support Fast to FTIH Studies

Molloy_MikeMike Molloy, MSc, Director, Analytical and Characterisation, Biopharm Process Research, GlaxoSmithKline

Two key deliverables for a successful path to First time in Human (FTIH) studies are the selection of a quality molecule and a stable cell line. This presentation will give an insight into how a combination of biophysical characterisation and accelerated stress delivers a much better understanding of product attributes during the discovery phase of drug development. This workflow is used for screening novel lead panel molecules with respect to their developability, ensuring that the right molecule is progressed to cell line development.

09:05 Efficient Identification of mAb Therapeutics with Optimal Developability

Yi_FangFang Yi, PhD, Principal Scientist, Biologics Discovery Sciences, Janssen Biotherapeutics, Johnson & Johnson

We share our strategies of implementing a matrix of high throughput orthogonal biophysical screening assays during early mAb discovery to identify candidates with not only the high-potency and specificity towards their biological targets, but also desired “developability”, e.g. feasibility of the manufacturability, good solubility and stability, and absence of off-target binding. Such strategies help minimize the downstream optimization efforts, leading to efficient lead selection with optimal functional and biophysical properties.

09:35 Problem-Solving Breakout Discussions (Foyer E)

Biophysical Characterization in Antibody Discovery

Moderator: Fang Yi, PhD, Principal Scientist, Biologics Discovery Sciences, Janssen Biotherapeutics, Johnson & Johnson

  • Which strategy is better? Large immunization campaigns coupled with early HTP screening OR small/moderate campaigns coupled with downstream optimizations.
  • What biophysical attributes are most important to ensure good developability?
  • Which assays are most efficient to funnel down large panel of candidates?
  • How predictive are the early HTP screening assays, and strategies to improve the robustness of the developability assessment?
  • New biophysical techniques and their potential impact

Developability Assays

Moderator: Michele Vendruscolo, PhD, Professor, Chemistry, University of Cambridge

  • Which are the most reliable developability assays?
  • Which is the optimal way to combine different developability assays?
  • Can in silico methods replace in vitro developability assays?
  • At which stage should these assays be used in the development pipeline?

10:30 Coffee Break in the Exhibit Hall with Poster Viewing (Pavilion 1)

11:15 Assessing and Addressing Biopharmaceutical Aggregation for Developability

Brockwell_DavidDavid Brockwell, PhD, Associate Professor, School of Molecular and Cellular Biology, University of Leeds

Protein-based biopharmaceuticals are susceptible to unfolding, mis-folding and aggregation by environmental perturbations that include hydrodynamic flow. Aggregation thus poses an enormous challenge to biopharmaceutical development, production, formulation and storage. To address this problem we describe an in vivo method to rapidly assess candidates for developability and an in vitro method to assess candidate manufacturability or process suitability for the manufacture of aggregation-prone biopharmaceuticals.

11:45 Purification Technologies to Tackle Complex Therapeutic Proteins during Lead Selection

Amsler_PhilippPhilipp Amsler, MSc, Functional Lead, Integrated Biologics Profiling, Novartis Institutes for BioMedical Research

Lead selection of therapeutic proteins 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, physicochemical properties, and other parameters of potential candidates. The presentation will provide an overview of the concept and focus on examples for different purification approaches enabling the production and characterization of complex protein formats.

12:15 Avidity Kills Cancer – The Biophysical Analysis of Bispecific Antibodies with the switchSENSE® Biosensor

Ulrich Rant, PhD, CEO, Dynamic Biosensors GmbH

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. 

Sartorius 12:45 Luncheon Presentation I: Screening for Inhibitors of T-cell Receptor Signaling

John O'Rourke, Head, Product Development, Cell Analytics, Sartorius

T cells play a critical role in the adaptive immune response.  In naive T cells, binding of the T cell receptor (TCR) to peptides complexed with major histocompatibility complex (MHC) triggers an intricate signaling mechanism leading to T cell activation, proliferation and production of cytokines.  Modulating the TCR signaling pathway using biologics, small molecules or genetic engineering is highly relevant to many therapeutic areas including cancer immunotherapy, adoptive cell therapy, vaccine development and autoimmune disease.

13:15 Luncheon Presentation II (Sponsorship Opportunity Available)

13:45 Dessert Break in the Exhibit Hall with Poster Viewing

Auditorium VI

14:15 Chairperson’s Remarks

Mike Molloy, MSc, Director, Analytical and Characterisation, Biopharm Process Research, GlaxoSmithKline

14:20 Optimising Developability – Learning from Experimental Data

Linden_LarsLars Linden, PhD, Head, Protein Biochemistry, Biologics-Research, Cell and Protein Science, Bayer AG

This presentation will discuss how to address developability early on in lead discovery and later in lead optimization phase. We will feed in experimental data and machine learning concepts, and bring in examples showcasing predictivity of higher throughput in vitro methods.

14:50 Rational Structure Guided Approaches to Biologics Design & Optimization

Dixit_SurjitSurjit Dixit, PhD, Vice President, Technology, Zymeworks, Inc.

Our growing understanding of disease biology and the need for personalized medicine is driving the design and development of fit for purpose, multispecific, multifunctional therapeutics. Protein engineering of biologics provides the opportunity to create such tailored therapeutic candidates and test their functional relevance. The presentation will highlight opportunities for rational engineering in the early stages of therapeutic design and its impact on developability of the drug candidates.

15:20 Using Molecular Modelling Tools to Optimize Ligand Presentation in Target Secretion Inhibitors (TSI)

Barata_TeresaTeresa Silva Barata, PhD, Senior Scientist, Product Design and Characterization, Neurology R&D, Ipsen Bioinnovation

Botulinum neurotoxins provide effective treatment for a wide range of neuromuscular and autonomic conditions, although their inherent toxicity limits use. Recombinant strategies allow development of next-generation BoNTs with new binding domains that provide novel and differentiated cell targeting and specificity characteristics and potentially lower toxicity. Here, molecular modelling tools are utilized to evaluate different engineering strategies for the presentation of a ligand targeting nociceptive neurons. Characterization of molecular interactions, together with molecular dynamics simulations, is leading to a rational and optimized approach for new TSI design and development.

15:50 High Affinity Guinea Pig mAbs Development: Application to Small Molecules Detection with a Multiplex Label-Free Platform

Yannick NIZET, CSO, Monoclonal Antibody Manufacturing Center, Synabs

16:20 Refreshment Break in the Exhibit Hall with Poster Viewing (Pavilion 1)

17:00 The CAMSOL Method of Rational Design of Protein Solubility

Vendruscolo_MicheleMichele Vendruscolo, PhD, Professor, Chemistry, University of Cambridge

CamSol is an in silico method developed for the rational design of mAbs developability. This method can provide accurate evaluations of key parameters of mAbs by replacing in vitro screening assays that are more demanding in both time and resources. CamSol thus enables the prediction of late-stage failures in early discovery phases.

17:30 Rational Design of Monoclonal Antibodies with High Developability Potential

WolfPerez_Adrian-MichelleAdriana-Michelle Wolf Pérez, MSc, PhD Student, Large Protein Biophysics, Novo Nordisk

We will present an in silico predictor assisted rational design method. This method can be applied for the rational design of developable antibodies, for the re-engineering of troublesome lead candidates, and for the early screening and ranking of variant libraries. Consequently, the method potentially increases the chances of a faster identification of lead candidates with high developability potential.

18:00 A Case Study for Developing a High Concentration Formulation for a Proof-of-Concept Clinical Trial

Lorène Bernasconi, Analytical Development Lab Manager, Novimmune SA

A monoclonal antibody (mAb) that binds and neutralizes human Toll-like receptor 4 is intended to be used for the treatment of immune-related disorders. After a successful intravenous dosing in the Phase I study using a low concentration formulation, a high concentration formulation suitable for subcutaneous administration was needed in order to initiate the Phase II clinical trial. The strategy developed to rapidly achieve this goal, including a description from the scale up for the manufacture to the adaptation of the analytical tools and optimization of the formulation, will be presented.

18:30 End of Optimisation & Developability