Optimisation & Developability banner

- 优化及发展性 -

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

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

MOLECULAR INSIGHTS DURING DEVELOPABILITY SCREENING

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.

14:15 Unspecific Binding and Self Interaction during Developability

Hackner_BenjaminBenjamin Hackner, PhD, Scientist, Physico Chemical Analytics, Protein Sciences & CMC, MorphoSys AG

Self-interaction and unspecific binding are important parameters to assess during developability of mAbs. We will demonstrate with a case study how self-interaction can be linked to high concentration liquid formulations and unspecific binding.


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 Prediction of Protein-Protein Binding Sites and Epitope Mapping

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

We present a method for identifying important interaction sites in protein interfaces and carrying out epitope mapping using MOE software. A case study is presented in which hydrogen-deuterium exchange data are used to extract key interactions from calculations performed on an ensemble of interacting chain models.

15:30 Sponsored Presentation (Opportunity Available)

15:45 Networking Refreshment Break


PLENARY KEYNOTE SESSION

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

19:30 End of Day

TUESDAY 13 NOVEMBER

07:45 Registration and Morning Coffee

DEVELOPABILITY ASSESSMENT TO GUIDE CANDIDATE SELECTION

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

10:30 Coffee Break in the Exhibit Hall with Poster Viewing

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


12:45 Luncheon Presentation I to be Announced


13:15 Luncheon Presentation II: A Quick Check of Protein Quality that will Improve Biotherapeutic Candidate Purification/Characterization Workflow

Peter Fung, Senior Manager, Product Marketing, Marketing, NanoTemper Technologies

Starting with material of questionable quality for protein purifcation and characterization leads to irreproducible or ambiguous results.Transitioning between upstream and downstream workflows can be challenging for bioprocessing researchers, especially when the quality of the sample material is not known.We offer a new platform that identifies sample quality and relative functionality in minutes complementing and guiding bioprocessing workflows-making go/no go decisions easy and quick-saving time, effort and producing more consistent results.

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

RATIONAL APPROACHES TO IMPROVE BIOLOGICS DESIGN, DEVELOPABILITY AND FORMULATION

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 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.


15:50 Presentation to be Announced

16:20 Refreshment Break in the Exhibit Hall with Poster Viewing

17:00 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.

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, PhD, 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

* 活动内容有可能不事先告知作更动及调整。

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