Katya Tsaioun
Chief Scientific Officer,
Cyprotex
Biography
Prior to founding Apredica, Dr. Tsaioun worked as a Group Leader at Surface Logix, Mitotix and NitroMed, where she developed in vitro ADME and in vivo DMPK programs for angiogenesis (oncology), CNS, metabolic disease, and infectious disease programs. Dr. Tsaioun earned her Ph.D. from Tufts University. Her Ph.D. thesis on effects of signal transduction and apoptosis factors in the rat brain was done under direction of Dr. Joseph in Neuroscience. Her post-doctoral training was at Harvard University Primate Center, working on in vivo and in vitro drug-dependence models with cannabinoid receptor and dopamine transporter systems. Dr. Tsaioun serves frequently speaks at international conferences on ADME and toxicology issues and serves on the Scientific Review Boards of Drug Safety Trust, Alzheimer’s Drug Discovery Foundation and International Retts Syndrome Society.
Abstract
New technologies for mechanistic toxicology in lead de-risking: CellCiphr™ Cellular Systems Biology (CSB™) approach
The cost of drug development is heavily influenced by compound attrition rate. For every drug that reaches the market, ~5,000-10,000 compounds have been tested pre-clinically. Drug-induced liver injury is a particularly serious problem in pharmaceutical industry, where in vivo preclinical testing has been shown to be insufficient in predicting mechanisms of human toxicity. This demonstrates the need for more accurate predictive liver toxicity models. Currently available and best validated in vitro ADME and Toxicity assays will be described. Ways they could be used as part of de-risking drug candidates will be discussed. High-content toxicology will be presented as developed in CellCiphr panels. The key questions that will be discussed will be:
- Which in vitro assays have enough validation behind them?
- How can the information obtained from the assays be used in conjunction with in vitro and in vivo efficacy and other ADME data to make decisions?
- How do we define safety window in the absence of human in vivo efficacy data?
In conclusion, case studies describing in vitro ADME-Tox strategies that de-risk drug discovery programs will be presented. Path forward will be discussed with new tissue models and mechanisms that the industry is building in order to develop more predictive tools to increase the success of drug-discovery programs.
