Thursday 24 May 2012- Day Two

• Application of “proven” animal PK and PBPK scaling approaches focusing on detailed case examples. 
• Successful selection of human doses for FIH studies and beyond
• Identification of food effect risks, and projections of food-effects via application of the BDDCS classes. 
• Modeling and simulation as meaningful tools in designing PK/formulation/ADME as well as species scaling toward FIH studies:  Specific formulation strategies, and proven modeling approaches that can be used when facing different BCS/BDDCS class compounds will be covered.
   

• › Tycho Heimbach, Fellow and Labhead, Novartis Pharmaceuticals Corporation

• The challenges of biologics, toxicological and pharmacological testing due to costs, species cross-reactivity, half-life and other ethical concerns
• Obtaining the maximum possible PKPD information from preclinical toxicological studies for regulatory & scientific requirements
• How rational scaling of this information to the human disease condition can critically impact the study design, doses and patient selections for early clinical studies/
• Brief outline of the preclinical pharm/tox testing strategy for biologics, some examples will be provided on how this information was maximally leveraged to help impact early clinical development strategy.

• › Balaji Agoram, Director, Clinical Pharmacology, MedImmune

• › Gerhard Gross, Head, Drug Metabolism, Lundbeck

•         A summary of the applications of microdose and microtracer approaches for exploratory clinical investigations will be presented
•         Phase 0, PK and DDI assessments will be included
•         Microtracer studies in early and late development for investigative clinical absolute bioavailability and assorted ADME assessments will also be explained
 

• › Graeme Young, Manager of Accelerator Mass Spectrometry, Drug Metabolism and Pharmacokinetics, GlaxoSmithKline Research and Development Ltd

o Drug and metabolite concentrations at the site of action vs in systemic circulation
o An improved connection between PK and PD
o Measurement of therapeutic target turnover in humans and its relationship to drugability
 

• › Professor Graham Lappin, Chief Scientific Officer, Xceleron

• Systems Pharmacology
• Translational PKPD for efficacy and safety
• Biomarkers and Bio-measures
• From target selection to POC
   

• › Piet H. van der Graaf, Senior Director Pharmacometrics, Global Clinical Pharmacology, Pfizer

• › Thierry Lave, Head of Modeling and Simulation, Non Clinical Safety, Hoffmann-La Roche

• › Jeffrey Heilbraun, MS, Director, Strategic Development, CoreLab Partners

• For drugs that increase the QT interval, it is now well recognized that potency at the hERG channel coupled with QT prolongation alone are not predictive of cardiac arrhythmia potential and that offsetting activity of a drug at the sodium and calcium channels must also be considered
• Significant progress has been made in developing nonclinical models for evaluating EAD and biomarkers for TdP potential that go beyond only looking at in vitro hERG and in vivo QT effects
• Approaches and considerations for evaluating the cardiovascular safety of drugs with mixed ion channel effects will be discussed and a case study example related to the assessment of several fluoroquinolone antibacterial agents will be presented

• › Gary Eichenbaum, Preclinical Development Leader/Research Fellow, J&J Pharmaceutical R&D, LLC

- Keep the end in mind
- Review the pharmacological effects observed in toxicology
- Check  those toxicology findings
- Be conservative in dosing
 

• › Malcolm Mitchell, Senior Medical Fellow, Clinical Pharmacology, Eli Lilly

- Risk mitigation by careful design and conduct of FiH studies
- Choice of study population: safety considerations vs. exploration of treatment effects

• › Beate Rohde, Head Development Clinical Pharmacology, Bayer Pharma

• › Michael Merz, Preclinical Safety, Translational Sciences, Novartis Institutes for BioMedical Research

- Regulatory background
- Rationale for starting dose determination
- PK/PD endpoints to support dose escalation
- Case studies
 

• › Antoine Deslandes, Scientific Advisor – Biotherapeutic Drug Disposition, Sanofi R&D