Real Patients & Their Virtual Twins: A New Paradigm for Personalized Drug Safety Assessment

Speaker(s): Mark Holbrook, Nikunj Patel, Sebastian Polak
Date: June 19, 2018
Time: 11 am EDT
Duration: 1 hour

A major challenge in developing efficacious and safe drugs is the ability to understand and effectively predict adverse effects of xenobiotic substances on complex biological systems early in the drug discovery process. An alarming fact is that thirty percent of adverse drug reactions (ADRs) cannot be predicted by current pre-clinical animal testing and existing modeling methodologies. Quantitative systems toxicology and safety (QSTS) modeling is an approach that can inform understanding of the mechanistic basis of ADRs and achieve more predictive and accurate risk assessments.

QSTS is a multidisciplinary approach which, at the juncture of Systems Biology with Toxicology and Chemistry, integrates classical toxicology with quantitative analysis of the molecular and functional changes that occur across multiple levels of biological organization. QSTS aims to characterize ADRs by describing modes of action as adverse outcomes pathways and perturbed networks versus conventional empirical end points and animal-based testing.

In this webinar, Sebastian Polak, Nikunj Patel, and Mark Holbrook will introduce the Cardiac Safety Simulator (CSS) platform and explain how they developed a QSTS model for citalopram to serve as a “virtual twin” and help predict the likely occurrence of cardiotoxic events in real patients under different clinical conditions. Citalopram is a widely prescribed antidepressant drug, which has been linked with cardiac toxicity especially at higher doses.

By attending this webinar, you will learn:

  • About the latest version of CSS platform
  • How QSTS models, with the appropriate drug and systems parameters, can bridge the gap between preclinical cardiac safety assessments and clinical toxicology results
  • How QSTS models, in combination with appropriate drug and systems parameters, can pave the way towards personalized safety assessments
  • How such an approach can be leveraged to inform predicting likelihood of drug-mediated renal, hepatic, and CNS toxicities in individual patients

About Our Speakers

Dr. Mark Holbrook is Certara’s Acting Vice President of Quantitative Systems Toxicology and Safety. Mark has extensive and broad experience of drug discovery and development gained from more than 28 years working for a range of companies across the biopharma spectrum; from small biotech (Celltech) and large pharma (AstraZeneca, Pfizer) to CROs (Covance) and consultancy. He has led projects from early target selection delivering molecules into development, through to proof of concept and regulatory filing. For the last 15 years, he has focused on non-clinical drug safety as the Global Head of Safety Pharmacology for Pfizer and more recently Covance where he was also the Chief Scientific Officer for Early Development. At Certara, Mark is leading Quantitative Systems Toxicology (QSTS) with the clear vision that it will significantly aid drug discovery and development helping projects be more efficient, make better decisions, and be more successful.

Nikunj Patel is a senior research scientist in Certara’s modeling and simulations group where he is leading oral and dermal absorption projects and is a member of the Cardiac Safety Simulator development team. He joined Certara in August 2011 and led the development of the physiologically-based IVIVC (PB-IVIVC) module of the Simcyp Simulator and the Pharmaceutics module of SIVA (Simcyp In Vitro (data) Analysis) platform. Before joining Certara, he spent three years at the life science innovation labs of Tata Consultancy Services as a research scientist, mainly working on pharmacokinetic/pharmacodynamic modeling and QSAR development for various ADMET properties. During his graduate studies, he used computer aided drug design (CADD) and molecular modeling to identify safe and potent novel anti-diabetic ligands.

Dr. Sebastian Polak is a Senior Principal Scientist at Certara where he is a member of the modeling and simulation group. He leads the development of cardiac safety modeling and simulation systems based on the biophysical models of human cardiac myocytes operating at the population level (CSS – Cardiac Safety Simulator). Dr. Polak is also a tenured Associate Professor in Biopharmaceutics at the Faculty of Pharmacy at Jagiellonian University in Krakow, Poland. Dr. Polak serves as a reviewer for multiple professional scientific journals and scientific book publishers. He has published over 40 peer-reviewed articles. He earned a DSc Degree in Biopharmacy from the Faculty of Pharmacy at Jagiellonian University Medical College in 2013. He earned a PhD from the Department of Toxicology, Unit of Pharmacoepidemiology and Pharmacoeconomics at Jagiellonian University Medical College in 2006. Dr. Polak earned a Master’s Degree in Pharmacy in 2000 from the Faculty of Pharmacy at Jagiellonian University Medical College.


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