Wednesday 23 May 2012- Biomarkers in early development

• Biologics in COPD need to focus on areas of high unmet need and economic burden and cannot use the paradigm used for bronchodilators in COPD
• Increasing understanding of this complex disease in animals and appropriately relating to mechanisms in human disease relevant to large molecules
• Optimal testing of the mechanistic hypothesis in early Clinical Development, and identifying patients most appropriate for studies
   

• › Donna Finch, Principal Scientist, within Respiratory, Inflammation and Autoimmunity, MedImmune

• Identifying stable gene lists for diagnosis, prognosis prediction, and treatment guidance of tumors
• Microarrays measuring differential gene expression and which identify robust biomarkers needed to relay true biological information
• Microarrays  method that can demonstrate gene list stability and predictive power and which is dependent not only on the size of studies, but mainly on the clinical phenotype
• How both stability and accuracy can be predicted by means of the expression profiles which are available from standard microarray data sets.

• › Andreas Schuppert, Director, Applied Sciences, Bayer Technology Services GmbH

• › Vincenzo Teneggi, Head of Early Development and Clinical Pharmacology, Roche China

• › Georg Wensing, Head Development Clinical Pharmacolgy, CV/PV, BayerHealthCare

Proof of Concept and the need to achieve this effectively·        

Overview of the use of complex adaptive trial designs in early phase drug development·        

The application of new adaptive methodology incorporating biomarkers for population enrichment·        

How biomarker-driven population enrichment provides robust decision-making in early phase trials
 

• › Dr Robert M. Miller, Chief Consultancy Physician, Aptiv solutions

• Why modify conventional Phase 1 trial design?
• Key elements of early diagnostic development
• Biomarker integration processes
• Informed consent issues
• Phase 2 deliverables in the era of targeted agents
   

• › Richard Buller, Vice President, Translational Oncology, Pfizer

• the principles of biomarkers for both safety and efficacy in regulatory toxicology studies for both small and large molecules to support FIH studies.
• the importance of pharmacodynamic biomarkers used in toxicology studies to support FIH studies.
• brief overview of classical and emerging biomarkers used in regulatory toxicology studies to support FIH studies.
   

• › Nicholas Buss, Toxicology Project Leader, MedImmune

• The promise of emerging safety biomarkers is to facilitate detection and monitoring of safety liabilities of drug candidates across preclinical species and human patients.  This will ultimately lead to better risk management of safety issues including understanding of human relevance of preclinical safety findings and full utilization of therapeutic index in target patient populations.
• The development of emerging safety biomarkers and their qualification has been a subject of extensive research efforts in industry, academia and regulatory agencies including variety of  consortia in US and Europe. 
• The presentation will discuss current status and case studies of application of emerging biomarkers of liver and kidney injury in preclinical and clinical drug development pointing out gaps that needs to be addressed to fully utilize their potential. 

• › Jiri Aubrecht, Senior Director and Group Lead of Safety Biomarker Laboratories, Pfizer

• › Anthony Gee, Professor of PET and Radiochemistry, Division of Imaging Sciences, Kings College London & Director of PET and Tracer Development, GlaxoSmithKline

• › Mary Savage, Senior Research Fellow, Merck

How can a QTc effect exceeding 10 ms be excluded in early clinical trials?
o Design considerations
o QT measurement techniques
What is a 'highly precise QT measurement technique'?
How can concentration effect modeling be used for QT assessment in early clinical trials?
What is the power of 'standard' early clinical trials to exclude a QTc effect of regulatory concern

• › Borje Darpo, Global Medical Director, iCardiac Technologies Inc