Opening Keynote presentation

Opportunities and challenges of drug discovery in the post-genomic era: The role of academic institutions in modern drug discovery

• How to utilize advances in basic science and translate the most exciting discoveries into marketable products
• Hear how the Vanderbilt VICB Program in Drug Discovery has established the infrastructure required to allow academic scientists to pursue the earliest stages of drug discovery while providing a mechanism to take this into an industry setting
• Learn from examples including the discovery of novel allosteric modulators of G Protein-Coupled receptors that may provide an exciting new approach for treatment of Schizophrenia and Parkinson’s Disease

Head of VICB Drug Discovery Program, Vanderbilt University

Session One: Innovation in drug discovery and Early development

CASE STUDY: How new discoveries have driven innovation on an ‘old’ target: The fall and rise of serotonin (5-HT1A) receptors

• Learn the rationale for drug discovery in psychiatric disorders including anxiety, depression and schizophrenia
• Hear about the current therapeutic agents targeted at 5-HT1A receptors: agonists and antagonists
• What is the importance of the diversity of subpopulations of these receptors in different brain regions, and the concept of ‘agonist-directed trafficking of receptor signaling’
• Discover the potential of a novel 5-HT1A receptor agonist, F15599, with preferential activity at these receptors in the frontal cortex to be an improved antidepressant.

CASE STUDY: Discovery and development of varenicline, ˇa4b2 nAChR partial agonist for smoking cessation

• Hear about the origin of the idea for a nicotine ACh receptor partial agonist for smoking cessation and the strategy of the project team to identify drug-like candidates, plus learn how the chemists found leads (high throughput screening vs. clues from Nature)
• Get an insight into the use of their in vitro and in vivo models, and the behavioral models used to predict efficacy
• Discover how preclinical data is translated to clinical findings and learn about the process of registration, approvals and labeling undertaken by

CASE STUDY: Discovering new aspects to old concepts in pain and neuroprotection

• Hear about the scientific background and limitations of testing the drug effects of specific compounds under evaluation
• Learn what positive impact there is when dedicated industrial research is combined with sponsored academic research to address these limitations
• Evaluate the validity of this concept for drug development in the broader context of the
  pharmaceutical industry in which improvements over existing drugs are incremental and major breakthroughs rare and risky

Session Two: Advances in drug development and design

The challenge of dose selection for proof of concept studies for novel drugs in CNS indications. How can we get it right?

• Examine the pros and cons of standard animal models for establishing dose for PoC studies with novel drugs, looking at new mechanisms and old precedents
• Understand when, why and what use are the results of PET and other forms of neuroimaging
• Find out what the role of toxicity margins in dosing is, and their relevance in early phase clinical development
  
• How to evaluate the usefulness of healthy volunteer pharmacodynamic studies for selecting PoC dosing regimens
  
• Learn about the design of dosing regimens for PoC study (e.g. multiple parallel group, MTD, single rising dose, adaptive design) and the advantages or limitations of each approach

WORKSHOP: Learn how to reconcile pharmacology and toxicology data when using different species and overcome the difficulty of estimating a therapeutic index

• What are the available strategies to circumvent the difficulty of allometric approaches which are often used to extrapolate pharmacological doses in species for which no data is available?
  
• Discover one way to overcome this problem through the implementation of a pharmacological test in the species retained for toxicological studies to establish a therapeutic index based on measured rather than extrapolated data
  
• Hear about the difficulties this has presented, and use the data presented to compare it to your efforts in estimating a therapeutic index

Head of Behavioral Pharmacology, Pierre Fabre

New solutions for improving the doseresponse relationship and speeding up the process during clinical phases

• Discover the usefulness of hormetic dose responses which are common and broadly
  generalizable in the biomedical sciences, including the neurosciences, being invdependent of biological model, endpoint and chemical class.
  
• Find out which CNS acting drugs commonly display hormetic dose responses affecting numerous endpoints, neuronal growth and survival, and numerous behavioral endpoints including anxiety, cognition, depression, and pain
• How the lack of recognition of hormetic dose responses in drug discovery and development may result in failure to identify the best candidate of therapeutic agents for numerous human diseases, and how to prevent this

Professor of Toxicology, University of Massachusetts

CASE STUDY: Convection Enhanced Delivery (CED): Challenges and opportunities

• Learn about CED, a highly promising clinical tool for delivering therapeutics to the Central Nervous System in a targeted and highly accurate manner with respect to dosing
  
• Explore the current state of this tool, in terms of clinical results, and discover the technical innovations being been made to improve this tool, including the development of guidance software and imaging agents
  
• Find out about the clinical targets currently subject to investigational activity and learn more about a clinical program platform that is utilizing the techniques combined with recent technical innovations

Session Three: Improving translational medicine and animal models

How the development of sophisticated translational tools could reduce risk and lower attrition rates to ensure a sustainable business model for innovation

• Understand why the reliance on single molecule targeted drug development represents a high risk – and an unsustainable business model – where the underlying etiology of a disease is not fully known
  
• Learn about the development of more sophisticated translational tools to help reduce attrition rates such as disease profiling, translational preclinical modeling, translational biomarkers, early clinical challenge studies and alternative IND strategies and adaptive design
  
• Get an understanding of new translational techniques from a case study in the use of
  multiplexed biomarkers in Alzheimer’s Disease (AD) following statin treatment

Director of Translational Medicine, Pfizer

Clinical Biomarkers in Drug Development: Manage the transition from discovery into clinical trials

• How to manage the transition from discovery into clinical trials and avoid the vast costs of attrition occurring during large scale clinical trials
  
• Create a checklist (by evaluating the several barriers needed to be overcome) to ensure that translational medicine is a practical and costcutting tool for you during the transition stage to first-in-man trials
  
• Discover methods for better assessments of proof of concept, focusing on some specific disease areas and drugs with a novel mechanism of action

VP Translational Medicine and President, Biomarker Alliance

CASE STUDY: Animal models in CNS drug discovery: Can they be predictive of human efficacy?

• Given that there are no animal models that represent all components of a given human CNS disorder, how can different animals be weighed up in terms of strengths and limitations so that they can be used effectively in CNS drug discovery?
  
• Gain insights from discussions on CNS drug discovery in the context of animal model's predictive capacity
  
• Successful preclinical data will be presented on a series of molecules that improve both rodent and non-human primate performance in cognitive tasks
  
• Listen to a breakdown of where the main challenges lie in using different animal models effectively for CNS drug discovery

Session Four: Effective Clinical Trial design

Clinical trial design: The challenges of conducting excellent clinical trials and how to overcome them

• Learn about the full range of considerations one must evaluate before designing a clinical trial and how these can impact on its management
  
• Find out how Cephalon has conducted successful clinical trials in the past, and what lessons they have taken from them
• Discover the length to which biometrics can be used to help design and manage fast and safe clinical trials

Speeding up the clinical trial process: Examine adaptive clinical trials and how they can reduce the need for larger patient numbers and help you reach maximum dose faster

• Learn from those pioneering this technique about the advantages and difficulties of implementing adaptive trials
  
• Hear specific examples from the lab of where it worked effectively and how this can be implemented elsewhere
• Discover by how much it could reduce costs and time in your clinical trials

AVP Adaptive Trials, Wyeth

CASE STUDY: How to bridge the gap between the bench and the bedside. The role of clinical science in drug delivery and bringing new drugs to market

• Effective ways to utilize advances in basic science and translate the most exciting discoveries into marketable products
  
• Learn how modern clinical methodology brings a new drug into the market and get a full comparative understanding of how both the American FDA and European EMEA regulatory bodies approve a new drug
• Discover what is meant by the Tysabri® paradigm, and what conclusions can be drawn for future drugs

Chairman of Neurology Department and Lead Clinician, Athens Naval Hospital

Expanding the knowledge on medical needs and the risk/benefit ratio of the CNS products through phase IIIb-IV clinical trials

• Hear the medical questions that are often unanswered when a CNS compound reaches marketing registration and how this can have adverse effects on its future
  
• How to address these questions through the product lifecycle and make sure your new drug works harder for you
• Can phase IIIb-IV projects contribute to expanding the knowledge on medical needs and the risk/benefit ratio, and if so how?
• Learn how to optimize design of phase IIIb-IV projects to meet your study objectives in the most efficient way

Clinical Project Leader, Elbion

CASE STUDY: Is there a way to stop clinical trials failing and could centralized ratings of symptoms be a solution?

• How can your company overcome the problem of clinical trial failures that are due to problematic assessment of symptoms by raters during subject interviews?
  
• What are the alternative methods that have been employed to beat poor interrater reliability, inadequate interview quality and rater bias?
  
• Learn how a pioneering new approach shows great promise for reducing placebo response and improved subject selection, and witness the data that backs this up

VP Clinical Development, Marinus Pharmaceuticals
Co-sponsored by MedAvante

Session Five: Cutting-edge clinical biomarkers

Issues in CNS Imaging: getting a "signal" and understanding it's relevance in disease heterogeneity

• Lessons learned in Alzheimer, multiple sclerosis, and stroke imaging
  
• Exploratory imaging vs. hypothesis-driven approaches
  
• Maximizing success; imaging all or some

Medical Director, Perceptive

New developments in imaging biomarkers for improved ability to test efficacy

• Discover the most promising new functional imaging biomarkers being used in clinical stages for both neurological and psychiatric disorders
  
• Hear how the best existing biomarkers have been successfully applied to new compounds in leading commercial companies
• Find out if these can be translated to help with your new compounds coming through to the clinical phase

Professor and Director fMRI Research Center, University of Columbia

Neuroimaging: Actualization of a technology not yet realized - its role in drug discovery and development

• Learn about ongoing advances in different neuroimaging modalities including positron emission tomography and magnetic resonance imaging, its role in the critical path initiative and potential impact in discovery and drug development
  
• Hear about the challenges in using imaging as a cost effective method in defining clinical endpoints and its role in the registration • Discover the potential of neuroimaging in the discovery of biomarkers and the potential applications to drug discovery and clinical trial design

VP ofImaging, Johnson & Johnson R&D

PANEL SESSION: An open debate on the utility of imaging techniques in drug development, focusing on:

• Its origins and how it has traditionally been perceived
  
• The current position of imaging in drug discovery, debating whether it is utilized enough across all spectrums of CNS diseases
• The future of imaging and what it may be capable of in the near future; plus what challenges lie ahead

Professor and Director fMRI Research Center, University of Columbia
VP ofImaging, Johnson & Johnson R&D
Plus! two more leading experts in the field