SBS 2009 - Technical Session Summaries

Advances In Screening and Automation
Anti-infective Drug Discovery
Drug Repositioning: New Uses for Old Drugs
GPCRs: New Targets & Modes of Action
Hit Identification Strategies
How to Define a Successful Candidate Profile
Nanotechnologies & Screening
Novel Assay Technologies
Protein-Protein Interaction Targets
Stem Cell Based Technologies
The Management of Chemical & Biological Samples
The Rise of Biopharmaceuticals
The Success of High Throughput Technologies in Delivering Drugs to the Clinic
Transporters & Ion Channels
Why Are So Few "Non-onco Kinases" Coming to the Market?


Advances In Screening and Automation: Technology, Tools, and Ideas - Anything New under the Lid?
Session Chair: Kevin Oldenburg, MatriCal, Inc., USA

In the 1990’s, innovations in assay development, compound handling, and automation were coming fast and furious.  However, as of late, the number of truly new technologies that have been appearing (hyped?) in the drug discovery and compound management arena has been more limited.  Walking the fine line between having a “product showcase” and a new technology symposium has always been a challenge.  This session will highlight new developments in Technology, Tools, and Ideas that will advance our field to the next stage.  Presentations will focus not only on new hardware but also new concepts or ideas that may be very early in development.  If you want to present a new instrument or technology that has been developed by your company, please feel free to submit an abstract.  However, we will ask that you submit the instrument/technology to an independent third party scientist (of our choosing) for outside review.  This scientist will present his/her finding at the session.  There will be a round table discussion at the end of the session to elicit from audience members what the real bottlenecks are in their research and float ideas on what can be done.


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Anti-infective Drug Discovery
Session Chair: Patrice Courvalin, Institut Pasteur, France

An important step towards the improvement of the quality of life in the last century has been the discovery of antibacterial agents, although in recent years their use has often been hampered by the continuous emergence of resistant strains. Traditionally, the new families of antibiotics were discovered by random screening of natural products and of chemical libraries followed by the continuous development of new generations of compounds to overcome the emerging resistance.
The aim of the pharmaceutical industry is obviously to be one step ahead rather than behind bacteria in this continuous race. Yet, for the last three decades most research has been dedicated to the improvement of existing classes of molecules rather than on the development of new families of antibacterial agents. For the development of new antibacterial agents, one should focus on molecules acting on new targets that escape resistance to other drug classes. This session is intended for researchers from pharmaceutical companies and academic groups whose aim is to contribute to the discovery of future antibiotics or is interested in the complex and important relationship between bacteria and antibiotics.

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Drug Repositioning: New Uses for Old Drugs
Session Chair: Jutta Reinhard-Rupp, MerckSerono International S.A., Switzerland

Drugs on the market, drugs in development or even failed drugs may experience a new lease of life, when looking more deeply into their mechanism of action. Repositioning may contribute to the life cycle of a marketed drug, it may help to identify new indications for compounds that were found to be safe in phase I, but not efficacious in phase II studies or later on. Increasing information and knowledge gain from in silico approaches, omics-technologies combined with attentive clinical observation and out-of the box thinking may provide interesting new avenues for known and tested compounds. The concept of repositioning also points out a tender spot in the pharma industry today - the desperate need to constantly deliver safe and efficacious drugs. Repositioning might rescue abandoned drugs, mainly through pharma industry/biotech partnerships.

In this session we will look at technology platforms that address systematic repositioning of drugs, we will hear examples from serendipity findings and we will learn how orphan indications and neglected diseases can benefit from halted drugs.

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GPCRs: New Targets & Modes of Action
Session Chairs: Alan Wise, GlaxoSmithKline, USA & Marc Parmentier,

G protein-coupled receptors (GPCRs) have been the single most productive target family for therapeutic drug intervention. Our understanding of the molecular pharmacology and function of GPCRs is rapidly progressing, providing novel and exciting opportunities to evolve drug discovery strategies at this target class. This 2-day SBS Session Meeting will focus on important aspects of GPCR function such as the structural aspects of assembly and relevance to activation and function, G protein dependent and independent signaling, trafficking, ligand-directed signaling, allosteric modulation, therapeutic relevance of recent GPCR deorphanisations and strategies to improve the tractability of screening for modulators at Family B and C GPCRs. This session will highlight novel strategies such as these to enable innovative drug discovery at GPCRs.

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Hit Identification Strategies: Developing the Right Tactics for the Right Program
Session Chair: Peter Hamley, Sanofi-Aventis, Germany

Identifying an appropriate chemical starting point for a given target is an essential prerequisite for success in Drug Discovery. Many factors can determine a successful strategy : the quality of the screening collection (both in terms of purity and physicochemical properties), the design of a full or biased collection, appropriate choice of screening concentration to match the nature of the collection (for example fragment screening), and the use of target knowledge in the design of compound libraries (for example by taking inspiration from natural products or biasing sets based on target class information). After well over a decade of diverse opinions and intensive experimentation it seems that some consensus is emerging as to the best strategies to choose for each target.

This session will focus on these key chemical strategies to enhance the success of hit identification, specifically the choice of appropriate physicochemical properties for screening collections and the application of knowledge-based approaches in compound library design.

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How to Define a Successful Candidate Profile
Session Chair: Tom Heigthman, (Affiliation Forthcoming)

Analyses of successful and failed drug candidates indicate that the two major causes for attrition are lack of efficacy and toxicity, both arising as a consequence of the poor predictivity of preclinical assays. In both areas, drug hunters are supplementing recombinant single target profiling with more complex, biologically relevant assays to drive lead optimization chemistry. This session will include talks covering recent analyses of reasons for attrition, feedback loops between clinical experience and preclinical screening strategies, and recent learnings on the use of high content screening techniques in predicting efficacy and toxicity, with the goal of enhancing the success rates of drug candidates through development.

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Nanotechnologies & Screening
Session Chair: Ian R. Hudson, GlaxoSmithKline, UK

This session will focus of innovative and emerging nanotechnologies that have a key role to play in developing assay formats 'beyond the microtitre plate'. The use of nanotechnology for drug discovery is being fuelled by the increasingly challenging conditions being faced by the pharmaceutical industry. Robotics, automation and the fine-tuning of microtiter plate assays have facilitated many advances in screening. After HTS, performing assays that vary component concentration or read at multiple time points is challenging at very low volumes. Focus is now shifting to validation and assay design areas, secondary screening as well as cell / in-vivo imaging. In addition, molecular diagnostics is becoming an integral part of drug discovery, disease management and therapy, patient population stratification, drug regimen selection, toxicity avoidance, therapeutic monitoring and detection of disease predisposition.

This session will aim to discuss whether nanotechnologies offer easy to use formats that could be utilized throughout the drug discovery process as well as in pharmacodiagnostics or theranostics.

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Novel Assay Technologies
Session Chair: Manfred Auer, affiliation - to be announced in August

Still the majority of all industrial small molecule drug discovery projects start with a plate based HTScreen of a large compound collection. Tool production and assay development are the core activities to prepare for a screening campaign. Besides of functionalization of the human genome, the strong focus on target validation, the increase of the chemical universe, it is the higher quality of lead compounds, which is expected to reduce attrition rates of compounds in development. To increase the mechanistic knowledge base of hit compounds new assay formats are needed for primary HTS and confirmation, for artefact free validation, and for multiparallel compound profiling. With the arising new scientific disciplines translational biology and medicine, systems biology, and synthetic biology, with strongly improved physical techniques for label free, and multicolour fluorescence based single molecule spectroscopy and high resolution imaging, with chemical and physical biosensor systems developed in unrecorded number, speed and complexity, with microfluidics and biochips becoming standard laboratory tools, the scientific discipline "drug discovery" has entered an exciting new area in which the term "assay" will become a different meaning during the next years.

This session will present cutting edge medical, biological, chemical, and physical assay technologies and new integrated multiparallel assay platforms with high potential to improve small molecular - and biological drug discovery.

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Protein-Protein Interaction Targets: New Approaches for Success
Session Chair: Martin Humphries, University of Manchester, UK

Targeting disease-related protein-protein interactions is one of the greatest challenges facing the pharmaceutical industry. Understanding the nature of molecular recognition processes and then developing approaches to perturb protein-protein interactions are top priorities.
A major hurdle is the development of synthetic strategies to create agents that can recapitulate natural hydrogen bonding, electrostatic and hydrophobic interaction patterns, and currently there are very few synthetic molecules with this capability. Recent advances have seen the targeted engineering of agents to enable recognition of sub-classes of biomolecules, including nucleic acids and carbohydrates, and attention is now focused on proteins. The synthesis of molecules that can recognize common secondary structural elements or large surface areas is an initial target for the field. The aim of this session will be to showcase the different strategies that are currently under development.

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Stem Cell Based Technologies: Current and Future Use in Drug Discovery
Session Chair: Maria Webb, Pharmacopeia, US

Despite many new breakthrough technologies including HTS and combi-chem, only 17 NMEs were approved by FDA in 2007, down from 53 in just 1996. An amazing 46% of clinical failures is due to lack of sufficient efficacy and an additional 25% of clinical failures is due to tox. Stem-cell technology has potential, not just in regenerative medicine, but in making models available for primary screens, secondary pharmacology, and toxicity evaluation. Differentiated cells derived from mouse ESCs are beginning to be utilized in high throughput screens, safety pharmacology and many other areas of drug discovery. To discuss how the current developments in stem cell biology apply to drug discovery, this session will review technical developments, including automated long term cell culture, different readouts, stem cell specific HCS, standardization of stem cells, defined cell medias. Additionally we will discuss the uses of stem cell biologies from tox profiling, target ID (RNAi, shRNA), to expression profiling of undifferentiated vs differentiated cells.

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Stem Cell Based Technologies: Current and Future Use in Drug Discovery
Session Chair: Maria Webb, Pharmacopeia, US

Despite many new breakthrough technologies including HTS and combi-chem, only 17 NMEs were approved by FDA in 2007, down from 53 in just 1996. An amazing 46% of clinical failures is due to lack of sufficient efficacy and an additional 25% of clinical failures is due to tox. Stem-cell technology has potential, not just in regenerative medicine, but in making models available for primary screens, secondary pharmacology, and toxicity evaluation. Differentiated cells derived from mouse ESCs are beginning to be utilized in high throughput screens, safety pharmacology and many other areas of drug discovery. To discuss how the current developments in stem cell biology apply to drug discovery, this session will review technical developments, including automated long term cell culture, different readouts, stem cell specific HCS, standardization of stem cells, defined cell medias. Additionally we will discuss the uses of stem cell biologies from tox profiling, target ID (RNAi, shRNA), to expression profiling of undifferentiated vs differentiated cells.

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The Management of Chemical & Biological Samples
Session Chair: Terry Wood, Pfizer Limited, UK

Not only the needs, but also the specialities of the sample management customer base have changed enormously over the past few years rapidly. Managers of sample repositories are called upon to provide a growing range of test materials to maximize the quality and quantity of information as early as possible, and not only to the drug discovery workflow. Small 'druggable' molecules continue to be made available, increasingly supplemented by fragment libraries, peptides, biologicals and nucleotides. Will we see a swing back to usage of the natural products compound managers were supplying a decade ago?

This diversity presents huge challenges to sample management teams, such that BioBanking, with its particular storage, supply and instrumental requirements, is often handled quite independently of more traditional sample supply. In addition, we are seeing an increased capability of academic and government institutions to maintain both biological and chemical inventories, and supply them to various testing laboratories. Furthermore, we must not overlook, nor underestimate, the challenges this diversity of sample supply presents to our IT and data management colleagues.

This session will focus on the broadening range of samples to be supplied and how compound management teams are adapting to meet the challenges presented.

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The Rise of Biopharmaceuticals
Session Chair: Sachdev Sidhu, University of Toronto, Canada

In the past decade, designer antibodies and proteins have revolutionized therapy for cancer and other devastating diseases. These biopharmaceuticals have played a leading role in therapeutic biotechnology by effectively targeting extracellular protein-protein interactions that remain recalcitrant to conventional small molecule approaches. The rise of biopharmaceuticals has been facilitated by advances in a broad range of technical areas, including protein structure analysis and engineering, understanding of the molecular basis for immunogenicity, and technologies for protein production, formulation and delivery.

This session will highlight technologies and fields of research that have enabled the current success of biopharmaceuticals and will explore new developments that promise to further expand the role of protein drugs as therapeutics for unmet medical needs.

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The Success of High Throughput Technologies in Delivering Drugs to the Clinic
Session Chair: Mary Jo Wildey, Symyx Technologies, Inc., USA

Research and technology investments over the past decade have introduced novel drug design methods, numerous high throughput technologies, new concepts in lead-likeness and drug-likeness, and substantial efforts to better understand the mechanisms by which pharmacological agents act. Many of these concepts and technologies are now established as integral components in all phases of the discovery process in pharmaceutical, biotechnology, and academic settings, enabling systematic research and evaluation of potential targets and therapeutic agents. Despite these efforts, the industry has been the subject of much debate as to the contribution of high throughput technologies to the drug market.

This session will provide perspectives on successes, failures, and lessons learned for several high throughput technologies used in the discovery processes.

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Transporters & Ion Channels: Challenges in Assay Development & Screening
Session Chair: Henning Vollert, University of Kiel, Germany

Despite their attractiveness as drug targets, ion channels and transporters (ICT) remain under-exploited target classes. This is in large part due to the labour-intensive nature of patch-clamp electrophysiology. The recent development of several automated electrophysiology platforms has greatly increased quality and throughput of electrophysiological recordings, allowing them to play a more central role in drug discovery. The session provides an update on the current state-of-the-art for automated electrophysiology platforms that are now available and critically evaluates their impact in terms of screening, lead optimization and in-vitro pharmacology in industry as well as academia. Besides the classical targets (particular: CNS and CV) the advent of novel technologies enable projects in almost all indications. The session will encourage scientists to discuss novel screening strategies as well as to start projects in (almost) un-touched indications like oncology, metabolism and inflammation. Another aspect will be the application of electrophysiology in other parts of the drug discovery value chain: One of the biggest hurdles in drug discovery are ADME/T issues. The session will show that a foresighted evaluation of leads (utilization electrophysiology) with regard to up-take mechanisms in several tissues can increase the efficiency of pharmaceutical projects significantly.

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Why Are So Few "Non-onco Kinases" Coming to the Market?
Session Chair: Swen Hölder, CRUK Centre for Cancer Therapeutics, UK

Several research programs in the pharmaceutical industry have aimed to discover and develop kinase inhibitors for non-cancer indications. Even though some of these candidates have reached clinical development, very few have made it to the market. This raises the question of whether the challenges inherent with the inhibition of kinases as a therapy for non-cancer indications can be overcome. In other words, can kinase inhibitors with sufficient selectivity and acceptable therapeutic windows be discovered? Are kinases appropriate points of therapeutic intervention or are they too centrally located within the signaling networks to be inhibited without severe side effects? Is the typical kinase inhibitor pharmacophore prone to interact with off targets like P450s, HERG or and ATP utilizing enzymes? The aim of this session is to shed light on these kinase-specific challenges and discuss potential solutions.

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