Lilly Discovery is exploring the use of cell based phenotypic and pathway assays to chemically interrogate complex biological systems composed of multiple or unknown biochemical components/pathways. Such Phenotypic Drug Discovery (PDD) approaches complement classical Target-directed Drug Discovery strategies. Potential advantages of PDD approaches include direct identification of cell active compounds, systematic inclusion of both known and unknown molecular components/mechanisms and interrogation of molecular targets in a relevant, cellular context. Concerns with cell based approaches include design of appropriate compound libraries, the statistical robustness and throughput of assays, and whether cellular assays can provide compound structure-activity relationships. This presentation is a status report on the use of PDD approaches at Eli Lilly and Company. Our experience to date indicates how multiplexed cellular imaging and the resulting compound activity fingerprints can be combined with advanced data analysis tools and computational hit expansion algorithms to identify compounds with known and novel mechanisms. Authors: Jonathan Lee, Jeff Sutherland, Tom Engler and Lou Stancato. BIOGRAPHY Dr. Lee is currently a Senior Research Advisor at Eli Lilly and leads a core Cellular Imaging group in Lead Generation-Optimization Biology. Dr. Lee’s group utilizes high content cell based assays to provide critical path assay support for projects from lead generation to candidate selection. Most recently, the potential impact and value of phenotypic lead generation assay strategies has been validated. Dr. Lee currently leads a group of scientists which is enabling a panel of phenotypic lead generation and secondary biochemical and cellular assays which represent therapeutic indications of long term strategic interest to Eli Lilly. These Phenotypic Assay Modules will be used to screen both internal Lilly compounds and novel chemical diversity from academic and biotechnology partners in a unique Pharma collaboration called PD2.

Despite immense investments in pharmaceutical R&D, lack of drug efficacy and presence of drug toxicity are two major reasons limiting R&D productivity. Systems Biology, uses a new perspective (integration instead of reduction) to study complex interactions in biological systems. Through integrated analysis of Mining, Modeling, Manipulation, and Measurements, applied systems biology has shown several successes in addressing major hurdles in both drug efficacy and toxicity. Using case studies of atherosclerosis and drug-induced liver injury, this talk will present the applications of systems biology to key stages of drug R&D, its significant impact and future directions.

The rapidly growing understanding of the molecular basis of disease pathology, aided by progress in genomics, genetics, and other “ ‘omic disciplines” provides us with numerous new insights into inter-patient difference and differences a more informative and accurate taxonomy of disease states. This understanding will allow us to devise new diagnostic tools and create more targeted medicines that are more effective and safer - this is what we understand as “personalised healthcare” (PHC) By taking the individual characteristics of patients and their diseases into account PHC has the potential to target medicines to those patients who are most likely to benefit from a therapy – thereby helping to avoid treating patients with medicines they are unlikely to benefit from and avoiding unnecessary exposure to the treatment’s potential side-effects. In some cases it will also be possible to identify patients who have a higher risk of suffering side-effects, allowing them to be treated with less risky therapies. This approach to healthcare promises many benefits: • Patients and physicians will benefit by being able to make safer, more efficacious and more rational therapy choices. The reduction of uncertainty related to the potential of response or risk from adverse events will likely improve patient compliance, duration of therapy and the patient-physician relationship. • Healthcare systems will benefit by reducing the burden of administering therapies to patients who have little or no chance of deriving benefit and by reducing the impact of avoidable adverse drug reactions. Whether or not this will lead to net cost savings by healthcare systems is difficult to say, as they will have to incur the cost of testing in order to reap these benefits – but PHC does represent a more rational and cost-effective approach to healthcare. • Drug companies also see some clear benefits from the PHC approach. The more rational use of medicines and the potential benefits for patients, physicians and healthcare systems means that it will be difficult for drug companies to register and market therapies which do not follow this approach. In addition, the PHC approach will likely allow many therapies to be developed which would not otherwise be developable. There is insufficient data to tell us whether or not PHC approaches will make drug discovery and development more efficient, but there are clear indications of the benefits of this approach in certain therapeutic indications. The systematic implementation within the drug discovery and development process requires new skills, competencies, infrastructures and processes and deep insights into the likely viability of a PHC approach in the targeted healthcare setting. This makes PHC approaches more suitable to certain healthcare settings and therapeutic areas than others.

Pharmaceutical R&D is a highly complex set of processes where uncertainty and risk persist throughout long discovery and development cycles. On average the development of safe and effective medicines takes 12 -15 years at a total cost that is now approaching $1 billion per product. Productivity for the industry as a whole, as measured as total cost per approved drug, has declined. Although many internal and external factors contribute to this lowered rate of productivity clearly one approach to address this issue is redesigning the R&D engine to increase the rate of innovation and learning, and the development of new products at a lower cost to meet medical needs. To address the speed of R&D and survival of drug candidates we have adopted a “systems” approach to accelerate scientific innovation, build efficient problem-solving and establish fast learning cycles. By adapting and applying the principles and methodologies of continuous improvement to the R&D environment we have begun to create a culture of “systems-thinking” that motivates teams, enhances problem solving and efficient data-driven decision making. BIOGRAPHY Andrew is a Senior Director in the Strategic Management Group at Pfizer Global Research and Development in New London, Connecticut, where his work is focused on approaches to enhance innovation and efficiency across Research and Development. He has 12 years management experience with Pfizer leading large multi-disciplinary departments in Drug Discovery and prior to that was researcher for over 12 years at Cornell Medical College, the American Cyanamid Company and Wyeth. Andrew earned his PhD in Chemistry from the University of Essex in the UK and did his postdoctoral research in the USA at Cornell University Medical College -New York Hospital with Professor Alton Meister.

The benefit/risk ratio is the yardstick in drug development to judge the potential of new molecules to become viable medicines with benefit to patients. Hence preclinical Safety (including not only the classical toxicology disciplines, but also safety pharmacology, immunotoxicology, drug metabolism and pharmacokinetics) is an important dimension when comparing similar molecules prepared in lead optimization programs and helps to select molecules with superior chance for a successful development. New in silico or in vitro methods in most safety areas are available or are being developed today allowing to assess, in short time, series of compounds for major liabilities (e.g., genotoxicity, major organ toxicities, teratogenicity, immune system perturbations, drug-drug interaction potential). Modern early safety evaluation takes advantage of these new tools to build a testing strategy beginning with target assessment and extending to lead compound optimization and selection of clinical candidates. Starting with in silico techniques (query of databases for detecting structural alerts; modeling and simulation) and in vitro methods (enzymatic or cellular models, preferably with humanized cell lines) including -omics technologies (e.g., toxicogenomics, metabonomics), applied methods become more complex (e.g., minitox screen, in vivo imaging) as the selection of potential drug candidates in a project narrows. These testing paradigms are devised to support science-based decisions, are targeted to the nature of the molecule under consideration (small molecular weight NCE; biological; siRNA therapies) and take all available previous experience with a compound class or target into account. Today in vitro methods are not ready yet to replace in vivo testing entirely because results are often still qualitative in nature and limited by the uncertainty of extrapolation to a whole organism and the human species. However, they allow to focus necessary in vivo evaluations to the relevant questions, support selection of the most promising clinical candidates, help in refining study designs and overall allow to reduce the amount of required in vivo animal and human testing.

As clinical safety and toxicity are among the major causes of late drug failure, it is of high importance to identify potential drug liabilities early in the drug discovery process. Broad-scale in vitro safety pharmacology profiling of new chemical entities is one key element allowing a rapid assessment of off-target activities which may be responsible for adverse effects at a latter stage. What is the impact for compound success? How best to use in vitro safety profiling data in the drug discovery process? How important is compound promiscuity during lead optimization ? Can in silico tools be developed to guide the chemist even earlier? All these questions will be addressed and illustrated. Authors: Jacques Hamon, Laszlo Urban, Steven Whitebread, Dmitri Mikhailov, Josef Scheiber, Kamal Azzaoui, Andreas Bender

The role of drug metabolism in contributing to the overall effects of drugs has long been recognised. Metabolites whilst often inactive, can sometimes contribute to the overall efficacy of the drug if they possess similar pharmacological activity, or indeed they may have pharmacological effects of their own unrelated to those of the parent. Similarly toxicity may result from metabolites rather than the drug. Whilst metabolites have always been taken into account during drug discovery and development the need for this has been further reinforced by the FDA guidance on “Safety Testing of Metabolites” published in February 2008. There are important consequences resulting from this document including perhaps, the need to obtain metabolite profiles in man earlier in development than has been the case up till now. The detection of unique human metabolites, or disproportionately high concentrations of circulating metabolites, may well have a significant impact on subsequent development. The implications of the new guidance will be discussed with respect to technologies that could enable early metabolic data from man. BIOGRAPHY Ian Wilson is a Senior Principal Scientist in the Dept of Clinical Pharmacology, Drug Metabolism and Pharmacokinetics at the AstraZeneca Research site at Alderley Park in Cheshire (UK). He trained as a biochemist (at UMIST) then undertook a PhD at Keele University. After postdoctoral work at University College London he joined Hoechst Pharmaceuticals where he worked in the areas of bioanalysis and drug metabolism. He then moved the ICI’s Pharmaceuticals Division, which then became first Zeneca and then AstraZeneca where he continued working in these areas in both discovery and development. His particular interests lie in the areas of bioanalysis, drug metabolism and metabonomics.

Preclinical models of drug-induced liver injury (DILI) are often not predictive of chronic liver pathologies in man. Even the most dedicated systems cover only the obvious endpoints such as necrosis, apoptosis, phospholipidosis and metabolic induced toxicity, leaving other mechanisms of injury uninvestigated. Furthermore, animal models often fail to predict DILI. The complexity of DILI with its multiple causes (idiosyncratic vs iatrogenic) and mechanisms involving cross-talk between many different cell types are the cause of this unpredictability. As a result it is difficult to identify populations who may be susceptible to DILI and DILI is often not identified until a drug has reached market, resulting in late-stage drug withdrawals. There is therefore a need for better DILI prediction. Identification of biomarkers to predict drug safety and efficacy and the development of an improved in vitro system which encompasses the multiple mechanisms of DILI are therefore essential and will be discussed in this session. BIOGRAPHY Jürgen Borlak was a Cancer Research Campaign-founded postdoctoral research scientist and in 1990 joined the Marion Merrel Dow Research Institute in Strasbourg, France, as Principal Investigator. In 1998, he was appointed Director of the Center of Drug Research and Molecular Pharmacology at the Fraunhofer Institute of Toxicology and Experimental Medicine; the centre focuses largely on the molecular effects of drugs and xenobiotics, using a wide range of methods and technologies in cell biology, genomics and molecular biology. In 2000, Jürgen Borlak was habilitated in pharmacology and toxicology and received the venia legendi at the Medical School of Hannover. In 2002 he was appointed as Full Professor to the chair of Pharmaco- and Toxicogenomics at the Medical School of Hannover. He was also appointed as Professor of Molecular Anatomy at the Medical Faculty of the University Leipzig in 2003. Jürgen Borlak is author of 183 original publications and 25 book chapters. He is reviewer and member of the editorial board for various scientific journals. Amongst others he is member of the Council on Basic Cardiovascular Sciences and an appointed expert of the World Health Organisation.

There is a significant drive within many pharmaceutical companies to expand their research activities outside their walls and create a network of alliances that cross the public and private sectors. But is this strategy working? In this talk we'll take a look at what should be considered before establishing a cross-organisational alliance, focussing on specific examples of alliances between big pharma and the academic sector as examples of what works and where the pitfalls are. We'll also assess the factors involved in building a successful collaboration, and consider an interesting model of alliance management designed to optimise return on investment.

Antibody fragments have been widely used as research and diagnostic tools for a number of years. With the success of ReoPro® and Lucentis®, the recent approval of Cimzia® in the US for Crohn’s disease, plus ongoing clinical trials with many antibody fragment-based drugs, they are now making an impact therapeutically. This presentation will review the variety of antibody fragments and alternative scaffolds currently being developed, will discuss some of their advantages and disadvantages compared to whole antibodies, and will assess their future potential. Examples will be taken from UCB-Celltech’s own experience with the clinical development of PEGylated Fab’ and F(ab’)2. BIOGRAPHY After earning a BSc(Hons) degree in Molecular Biology at Edinburgh University UK (1987), Dr Popplewell obtained a PhD from Southampton University UK in the field of protein engineering (1991). He held Post Doctoral positions at the Centre for Genome Research (Edinburgh) and at Southampton University Department of Biochemistry, before joining what was then Celltech in 1993. During his 15 years at Celltech (since 2004 UCB Celltech), Dr Popplewell has played a role in developing their antibody humanisation and E. coli expression technologies, working on several clinical candidates including Cimzia and CDP791. He currently leads the V-Region Discovery and Engineering department at UCB’s Slough Research centre.

Companies in the pharmaceutical and biotechnology sector are facing a crucial challenge, the efficient translation of innovative ideas into products and services. Over the past several years, the time and money required to fully develop a research idea into commercial product have substantially increased. When coupled with the high and increasing risk of failure during preclinical or clinical development, the financial model of internal/self-sufficient funding and product development is rapidly becoming unworkable. A partial solution to this problem can be achieved through collaborative actions between two or several companies. This talk will touch on a spectrum of company-to-company collaborations, e.g., pre-competitive consortia, strategic partnerships, and mergers and acquisitions, with consideration of some of the conditions, constraints and potentially positive outcomes from these interactions. BIOGRAPHY Dr. Bruce M. Pratt is Vice President, Science Development, for Genzyme Corporation, with responsibilities in the identification and evaluation of early stage opportunities (primarily therapeutic products) and proactive, selective outreach activities to the academic and biotechnology sectors. He has worked for Genzyme for 20 years, initially in positions of increasing responsibility in Cell & Protein Therapeutics Research & Development, culminating as Sr. Director of Cell Biology. From 2002 through 2004, he was based in one of Genzyme’s European offices, identifying early stage European research and product opportunities as well as developing relationships with biotechnology companies and academic centers of excellence. Returning to the United States in July 2004, he has continued his role in early stage opportunity identification and outreach to the biotechnology sector. Prior to Genzyme, Dr. Pratt worked at Collagen Corporation and Celtrix Pharmaceuticals in Palo Alto California. He earned his Ph.D. from Michigan State University and was a post-doctoral fellow at Yale University School of Medicine, Department of Pathology.

Dr. Jonathan Mason is Chief Scientist, Predictive Technologies & Drug Design and Divisional Director of Computational Chemistry & Structural Biology at Lundbeck Research Denmark at Copenhagen. He has previously led teams involving Computational Chemistry, Structural Biology, Medicinal Informatics and Knowledge Discovery at Pfizer in the UK (Executive Director MISD) and Bristol-Myers Squibb in the US (Director SB&M), following many years at Rhône-Poulenc Rorer (now Sanofi-Aventis) in the UK, France and US building and leading Computer-Assisted Drug Design teams. Dr. Mason started his career as a medicinal chemist, and has 28 years of pharmaceutical drug discovery experience. He has been a pioneer in the development and use of 3D pharmacophore fingerprint methods, together with other molecular similarity and diversity approaches, for both ligands & protein targets (e.g. for virtual screening, ligand docking, target-class library design, HTS analysis). Recently he has driven the use of biological fingerprints to tackle attrition-related problems including lead selection / differentiation and enable new chemogenomic approaches. Dr Mason is also a member of the Scientific Advisory Board of Heptares Therapeutics (GPCR structure-based drug discovery).

Dr Michael Allen graduated with a degree in Pharmacology from the University of Bath before conducting his Ph.D. research on the role of inositol phosphate second messengers in smooth muscle contraction. Michael has spent the last 17 years at GlaxoSmithKline involved in drug discovery, from high throughput screening through to preclinical development activities, and led GSK’s project on pretern labour (which is now in phase II trials) from project proposal through to preclinal development. For the last four years Michael has specialised in the application of industrial techniques, particularly Lean and Six Sigma, to laboratory environments. Michael will be leaving GSK in the new year to set up his own business specialising in training, mentoring and consultancy in the application of Lean and six Sigma to lab and R&D environments.

Despite immense investments in pharmaceutical R&D, lack of drug efficacy and presence of drug toxicity are two major reasons limiting R&D productivity. Systems Biology, uses a new perspective (integration instead of reduction) to study complex interactions in biological systems. Through integrated analysis of Mining, Modeling, Manipulation, and Measurements, applied systems biology has shown several successes in addressing major hurdles in both drug efficacy and toxicity. Using case studies of atherosclerosis and drug-induced liver injury, this talk will present the applications of systems biology to key stages of drug R&D, its significant impact and future directions

In this presentation, Dr. Deroose will share his views on outsourcing medicinal chemistry at J&J. A historic perspective will be given as outsourcing has moved from synthesis and scale up of “simple” building blocks to strategic partnerships in drug discovery. Over the last decade, Dr. Deroose has built a global network of drug discovery service providers and CROs in the area of medicinal chemistry, enabling biology and drug metabolism. Some key elements of the current strategy in outsourcing medicinal chemistry will be outlined with an emphasis on fully integrated services supporting therapeutic areas at J&J. BIOGRAPHY Dr. Deroose started his professional career in 1996 at Johnson & Johnson in Belgium at Janssen Pharmaceutica as a medicinal chemist in the field of Inflammation, Allergy and Asthma. He has been a key contributor to several New Molecular Entities and clinical candidates. Dr. Deroose has more than 25 publications and patents. Since 2000, Dr. Deroose has also taken on additional responsibilities; Total Quality Management, Molecular Design and Chemo-Informatics and has become involved in external partnerships and collaborations. As of 2002, he is responsible for the Centre of Excellence in global compound acquisition and external medicinal chemistry for all Research and Early Development (RED) sites in US and EU at J&J. In 2007, in addition to his leading role in outsourcing research, he has been leading an internal team of scientists developing an integrated research platform focusing on a kinase directed proprietary technology. He has been running a portfolio of drug discovery programs. In 2008 this technology platform is being created as a spin-off. Dr. Deroose has been a key leader at J&J in developing and implementing a strategy in outsourcing research. He has built over the years a global network of drug discovery service providers and CROs in the area of medicinal chemistry, enabling biology and drug metabolism. He presently manages approximately 100 external full time employees.

Dr Nicola Richmond is currently a principal scientist in the Computational and Structural Chemistry group at GlaxoSmithKline, a post she has held for over four years. Prior to joining GSK, Dr Richmond was the Tripos Research Associate in Peter Willett's group, at the University of Sheffield, where she developed a novel, now commercialised methodology for the automated alignment of molecules in 3D. She joined Sheffield having spent nearly two years with the Statistics and Modelling group at Unilever R&D, initially based in Port Sunlight then latterly at the Centre for Nanoscale Science, University of Liverpool. Her career path has been somewhat unconventional as she is educated to PhD level in pure mathematics and to MSc level in computer science.

Dr. Samarsky earned a Ph.D. in biochemistry and molecular biology from the University of Massachusetts, Amherst, in 1998. From 1998 to 2001 he was the H. Arthur Smith Fellow for Cancer Research at the laboratory of Dr. Michael Green, a Howard Hughes Medical Institute investigator at the University of Massachusetts Medical School. From 2001 to 2003, Dr. Samarsky led business and technology development at Sequitur until the acquisition of this company by Invitrogen. From 2003 to 2005, Dr. Samarsky served as Business Development Manager at Invitrogen, where he focused on promoting RNAi and other genomics technologies. Most recently, Dmitry Samarsky served as Director of Technology Development at Dharmacon/Thermo Fisher, where his team was responsible for promoting Dharmacon's RNAi program worldwide. In addition, he established and led an RNAi applications laboratory. Dr. Samarsky has authored numerous research articles, reviews and book chapters in the field of RNA.

In the context of higher clinical failure rates and increasing number of compounds for biologics such as i.e. monoclonal antibodies or leukine muteins it becomes very important to efficiently manage technical development activities including clinical material production. Several strategies including bench marks used by big pharma and biotech companies as well as suited for biotech SMEs will be summarized focussing on lean processes, particularly in the early phase to clinical proof of concept (PoC). The pro and cons of such modern “back-loaded” development approaches compared to the classical continuous or front-loaded development will be discussed in detail.

Five years ago most scientists did not consider low molecular weight fragments (MW = 120-250) with correspondingly low binding affinities of only mM to uM to be attractive starting points for drug discovery programs. However, today there is widespread acceptance that these fragments can be progressed into nM lead series and on into clinical candidates. A detailed structural understanding of the binding interactions between the fragment and its target protein utilizing X-ray crystallography or NMR is critical. An example from Astex’s laboratories of a fragment derived compound that is in oncology clinical trials will be discussed. BIOGRAPHY Andrew Woodhead is Associate Director of Chemistry at Astex Therapeutics. He has been with Astex since 2001 and has experience of fragment hit identification and structure based drug design for a number of targets including the oncology targets CDK2 and HSP90. He began his medicinal chemistry career with Wyeth in 1992 working on CNS disorders such as migraine and depression. In 1994 he joined Roche to focus initially on inflammatory diseases and then moved to the virology department, before finally joining the lead generation chemistry group. He carried out his academic studies at De Montfort University, Leicester.

In 2007 Pfizer created an Indications Discovery Unit (IDU) to add value to their extensive portfolio of development compounds by identifying and advancing opportunities for these compounds beyond their initial indications. This cross-therapeutic area team quickly defined a system to identify additional indications that employs both serendipity- and knowledge-based approaches. In the year since its inception the IDU has delivered value in several areas, including new product opportunities as well as the development of novel enabling tools. Importantly, that the success of this endeavor is largely a result of the highly-integrated nature of IDU collaborations, both with internal Pfizer and external partners, will be described. This presentation will use specific examples to highlight the progress, challenges, lessons learned, and potential future directions. BIOGRAPHY - Dr. Dean Welsch is a Research Fellow in Pfizer’s Indications Discovery Research Unit which is headed by Dr. Don Frail. Dr. Welsch is a key contributor to the strategic design and implementation of this paradigm-shifting group, whose remit is to fully capitalize on Pfizer’s unparalleled Development portfolio by identifying and advancing novel opportunities for compounds beyond their primary indications. Prior to establishment of the Indications Discovery Research Unit in 2007, Dr. Welsch was a Senior Director in Biological Sciences at Pfizer with responsibility for programs in Inflammation, Allergy & Respiratory, and Immunology. Inspired by the opportunity to deliver through innovation, Dr. Welsch brings his 18+ years of experience, broad scientific and operational expertise, and creativity to advance the objectives of the Indications Discovery Research Unit. Today Dr. Welsch is here to briefly provide a status update of the group’s accomplishments since inception, highlighting progress, challenges, and potential future directions.

Clare has worked for AstraZeneca for the past 6 years. She started working in the DMPK section of the CVGI RA 2 years ago. In her present role, Clare provides support to a variety of diabetes and obesity projects as a DMPK representative as well as maintaining a presence in the lab as an expert bioanalyst. With this experience in mind she was selected to lead the first Lean Six Sigma project to be run in the R&D setting, at Alderley Park. As will be discussed today, this was a resounding success. The achievements afforded by this project have contributed to the initiation of a multitude of Lean Six Sigma projects across the company, many of which Clare has, and continues to be, on hand to assist with.

Cell based assays have become the method of choice for compound screening for drug discovery. The industrialisation of these assays has involved the adoption of a number of technologies and working practices common to the manufacturing industry to reduce variability and costs. Examples of these include automated methods of cell culture, the use of cryopreserved cells and the use of simple assay protocols to improve assay performance. We will use as a case example how the implementation of Aequorin technology together with the adoption of cellular manufacturing principles has reduced cost, and improved quality of assays used for drug discovery. BIOGRAPHY My section is focused on delivering compound profiling data using high-throughput cell-based assays to support Hit to Candidate SAR drug discovery programs. My main area of scientific expertise lies within the GPCR area and my previous achievements in GSK have involved GPCR deorphanisation, oligomerisation and novel mechanisms of function. Prior to joining GSK, I held a Post-Doc position with Graeme Milligan at the University of Glasgow studying molecular pharmacology of GPCR function. I originally graduated with a Biochemistry Hons Degree from University of Leeds and then followed this up with a PhD at the same institution studying G-proteins in plants.

Andrew joined SmithKline Beecham, Harlow in 2000, working on kinase inhibitors for fibrosis. From 2001-2008 he has been a Research Leader in the Psychiatry Centre of Excellence for Drug Discovery, working on New Generation Atypical Antipsychotics as well as other Programmes targeting schizophrenia and bipolar disorders. His current role is as Programme leader for an effort targeting cognitive disorders within the Neurosciences Centre of Excellence for Drug Discovery.

The so-called “4th hurdle” is now a reality in the majority of countries. Patient access to a new medicine is now dependent of the demonstration of the value of a medicine to pricing and reimbursement authorities and/or health technology assessment bodies. This value demonstration is required at a national level but increasingly more often also at a regional and even local level. This segmentation of the payer audience introduces a high level of complexity in terms of data and evidence requirements for value demonstration of a product. It has therefore become crucial to provide guidance on the payer data requirements for “value demonstration” and insight on the continuous evolving Payer context during a product development in order to ultimately guarantee the access of the medicines to patients. This session will provide a perspective of when these considerations should be taken during the development of medicinal products, the payer decision making process in a “real life” context, inputs and outputs to be considered in the research development plan, additional evidence required for value demonstration and future trends.

Organic growth towards a “single-stop-shop” partner where clients can satisfy most of their needs, including computational design, chemical synthesis, biochemical and ADMET/PK profiling, drove NiKem Research activities and ensured success in the past seven years. However, technology platforms are not per se enough to be successful; grey-haired, well-trained medicinal chemists do have a unique capacity to translate ideas into clinical development candidates with greater chances to survive through development. Add to this “in house” profile a sustainable “hybrid” proposition, exploiting competitors from Asian countries to provide a 40% discount on prices in a highly productive NiKem-driven, IP-secure and quality-respectful scenario.

The session will cover the technical fundamentals of PET, SPECT and CT as they are related to pre-clinical imaging. Benefits and limitations of the different modalities as well as their infrastructural requirements for the use in pre-clinical research will be discussed and examples of their use will be provided. Special attention will be given to the translational role of those modalities both in bridging the in-vitro to in-vivo as well as the pre-clinical to clinical gaps. BIOGRAPHY Dr. Haemisch, Vice President Imaging Technologies at Bioscan Inc. is responsible for the expansion of the pre-clinical imaging portfolio. Prior to his current position he worked with Philips, ADAC Laboratories and General Electric as product and marketing manager in clinical and pre-clinical imaging. He acquired special expertise in nuclear imaging (SPECT & PET) and in particular in the technology development for high resolution pre-clinical imaging.

In Vivo imaging of biomarkers can dramatically increase the efficiency of the drug development process. These biomarkers can be used to characterize target engagement as well as pharmacokinetic and pharmacodynamics modeling in both pre-clinical and clinical studies. The translation of pre-clinical results to clinical endpoints remains a challenge in drug development. Of critical importance to successfully bridge this gap is to closely align pre-clinical and clinical studies where possible. Maintaining a consistency in the imaging protocol and biomarkers used in both pre-clinical and clinical studies aids this translation greatly. In this workshop roundtable session, participants will discuss factors influencing decisions that are made when incorporating non-invasive, in vivo imaging in drug development such as: • The role of radiotracers and contrast agents for the visualization of targets, tissues, and/or organs • Development of consistent imaging protocols and biomarker applications that translate from pre-clinical to clinical studies • Examples of non-invasive, in vivo imaging applications in drug development in oncology, CNS, arthritis, cardiology, and early toxicity studies • Case studies illustrating advantages of SPECT over PET small-animal imaging for oncology drug discovery and development BIOGRAPHY Jeffrey Norenberg, Pharm D, is an Associate Professor and Director of Radiopharmaceutical Sciences, Director of the Keck-UNM Small Animal Imaging Resource and the Associate Director of the New Mexico Center for Isotopes in Medicine at the University of New Mexico Health Sciences Center. He has expertise in the clinical pharmacology and targeted therapies in oncology focusing on targeted delivery of radiopharmaceuticals for diagnosis and therapy and the translation from basic to pre-clinical and clinical research. Dr. Norenberg has also developed a novel approach to using alpha-emitters for targeted therapy. Dr. Norenberg maintains a smallscale cGMP laboratory to provide novel parenterals for clinical studies.

Biobide offers services for mass testing of drugs from Pharma and Biotech, providing a differentiating factor with respect to mass drug testing done so far in vitro. Biobide conducts testing on the in vivo model of the zebrafish embryo, providing more information to test the compound in a living organism (vertebrate) rather than an isolation cell. The use of this animal model has several advantages: embryos are transparent, allowing the display of the bodies of animals; very rapid organogenesis, using small quantity of drug to be tested; the test accurately reproduces what happens in a living organism to administer a drug as they show a genetic homology of over 85% with respect to men, allowing them to study human diseases; and the high number of embryos obtained in each start, gives us the ability to test large numbers of compounds. Inside implementation of the 3R’s (Refining, Replacing and Reducing animal use in toxicity screenings). Also, thanks to the massive automated testing platform at Biobide, we increase the reliability of the tests, compared with those carried out manually. This reduces the time and cost of the Drug Discovery process around 20%. BIOGRAPHY Carles Callol received his B.S. in Biochemistry degree from the University of Barcelona. He worked in the laboratory of Integrative Biochemistry and Cancer Therapy in the University of Barcelona until he joined in 2003 to the Gene Expression Laboratory at the Salk Institute, where he focused his research in studying zebrafish embryological processes involved in heart development. His main research interest is the application of zebrafish in the drug screening process, to which he has dedicated the last 2 years in Biobide. BIOGRAPHY Carles Callol received his B.S. in Biochemistry degree from the University of Barcelona. He worked in the laboratory of Integrative Biochemistry and Cancer Therapy at the University of Barcelona until he joined the Gene Expression Laboratory at the Salk Institute in 2003, where he focused his research in studying zebrafish embryological processes involved in heart development. His main research interest is the application of zebrafish in the drug screening process, to which he has dedicated the last 3 years in Biobide.