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
Day 1 | Day 2 | Download Brochure | Interactive Speaker Biographies
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.
MONDAY 12 NOVEMBER
12:00 Conference Registration (Foyer C)
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
Hubert 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.
14:15 POSTER HIGHLIGHT
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
Mike 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)
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
Day 1 | Day 2 | Download Brochure
TUESDAY 13 NOVEMBER
07:45 Registration (Foyer C) and Morning Coffee (Foyer D)
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
Mike 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
Fang 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
David 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
Philipp 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.
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
14:15 Chairperson’s Remarks
Mike Molloy, MSc, Director, Analytical and Characterisation, Biopharm Process Research, GlaxoSmithKline
14:20 Optimising Developability – Learning from Experimental Data
Lars 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
Surjit 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)
Teresa 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
Michele 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
Adriana-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
Day 1 | Day 2 | Download Brochure