08:00 Pharma IQ Welcome And Chairperson’s Opening Address

08:50 A Medicinal Chemist’s View Of Predictive Toxicology And Strategies To Avoid Toxicological Risk

• Medicinal chemists are increasingly attempting to avoid toxicological risk at the point of new compound design or in early screening and SAR studies
• In some areas such as hERG there is good knowledge of the chemical features which lead to activity and ways to reduce this liability
• There is also an increasing awareness of structural properties that lead to increases in the general risk of toxicological findings
• However while we have made progress there are still many gaps in our ability to avoid toxicological risk
• The talk will discuss the current situation with regard to the above points, how these are being addressed in AstraZeneca, and likely future developments

Dr Richard Luke
Principal Scientist
AstraZeneca

09:30 Outlook To The Future Of Regulatory Guidelines For Safety Testing: A UK Regulatory Overview Of Predictive Toxicology In 2011

• Understanding the role of the MHRA in safety testing
• Update on current safety testing guidelines in the UK
• Implementing scientific advice and MHRA recommendations
• Future perspectives: what does the future of scientific and regulatory predictive toxicology look like?

Dr David Jones
Expert Pharmaco-Toxicologist
MHRA

10:10Predictive toxicology: How a CRO can help reduce late stage failures

Nick Pearson
Lead Investigate Toxicology
CIT

11:10 Understanding Metabolite Mediated Cell Toxicity To Enhance Hazard Identification And Risk Assessment

• Current understanding of the role of metabolism in toxicity, focusing on adverse drug reactions
• Overview of available in vitro and in vivo preclinical models that can be implemented in your predictive toxicology approach
• Case studies highlighting the value and limitations of individual models for hazard identification and risk assessment to boost the accuracy of toxicity testing

Dr Gerry Kenna
Principal Scientist in Molecular Toxicology
AstraZeneca

11:50 Nephrogenic Systemic Fibrosis (NSF): Lessons Learnt With Regard To The Predictive Capabilities Of Preclinical Studies

• The clinical picture of NSF - a rare disease associated ith the administration of Gadolinium-containing contrast agents (GBCAs)
• Insights into preclinical findings after administrations of GBCAs
• Exploring hypotheses on the pathomechanisms based on preclinical results
• Can the preclinical results contribute to risk assessment and management of NSF?

Marian Raschke
Investigational Toxicology
Bayer Health Care

12:30 MetaMap Tox® – a novel metabolite profiling based tool in Pharma safety assessment

Dr. Hennicke Georg Kamp
Group Leader, Dep. of Experimental Toxicology and Ecology
BASF SE Toxicology and Ecology / Metanomics Health

14:10 Re-Evaluation Of The National Toxicology Program (NTP) Mouse Lymphoma Tk Assay (MLA) Database Using Current Standards

• According to the NTP the mouse lymphoma assay has a large number of positive responses for chemicals that are not rodent carcinogens
• Standards for interpreting MLA data have changed substantially since the NTP database was created
• Using current standards the majority of chemicals called positive by NTP are not actually positive
• A large portion of the NTP MLA experiments do not meet current acceptability criteria
• A large portion of the NTP MLA chemicals cannot be evaluated as positive, negative or equivocal using current standards
• Understanding what the conclusions of the reevaluation of the NTP means for your predictive toxicology approach

Dr. Martha M. Moore
Division of Genetic and Molecular Toxicology
FDA

14:50 What Is The Real Incidence Of Positive Results In The Mouse Lymphoma TK Assay (MLA) In Pharmaceutical Screening?

• The mouse lymphoma assay (MLA) has been reported to have a false positive rate of more than 50%
• In pharmaceutical screening at AstraZeneca, only 15% of all drugs tested in the MLA are positive
• The vast majority of these positives are likely to be due to the pharmacological target of the drug, hence cannot be described as ‘false positives’
• In reality, when used in a pharmaceutical screening paradigm, the ‘false positive’ rate of the MLA is as low as 5%
• Impact of the low ‘false positive’ rate of the MLA on your safety screening

Dr Mick Fellows
Safety Assessment
AstraZeneca

16:00 Assessment Of Cardiac Liability Using Stem Cell Derived Cardiomyocytes

• Definition of cardiotoxicity: safety pharmacology vs. cardiac-specific cytotoxicity
• The optimal cell model for assessment of cardiotoxicity: benefit of stem cell derived cardiomyocytes
• Production and characterization of stem cell derived cardiomyocytes
• Use in safety pharmacology: hERG • Arrhythmias • APD prolongation
• Use for cardiac cytotoxicity: cell viability • mitochondrial toxicity
• Compounds affecting cardiomyocytes: cardiac liability of TKI

Dr Silke Schwengberg
Senior Scientist, Head of Laboratory
Axiogenesis AG

16:40 Interactive Panel Discussion With The Drug Safety Executive Council: Predictive Toxicology Tools: Reducing The Risks A Ssociated With The Adoption Of Novel Technologies

• Do you see the role of in vitro toxicity assays increasing in importance and frequency prior to animal toxicity testing? What in vitro assays are most often used now (other than ADME) prior to animal toxicity testing?
• Would you only implement a technology that you would run in-house?
• How does potential regulatory acceptance factor into a decision to adopt a new technology (--or-- does good science triumph over regulatory uncertainty)?
• To what extent are Stem Cells being used for in vitro cell-based assays to identify drugs with higher efficacy and minimal toxicity? What are the barriers that must be overcome for this approach to accelerate progress?
• To what extent do you need to quality/validate a novel technology so that your project team will accept it?
• At what level of management is the decision taken to evaluate and adopt a new technology?

Facilitated by:

Dr. Ernie Bush
Director, Collaborative Projects
Drug Safety Executive Council

17:20 Chairperson’s Closing Remarks And Close Of Day One