DMPK for Targeted Tissue Delivery: Solutions for the Most Challenging Part of Outsourcing

Evaluating therapeutically relevant disposition in target tissue is often a pivotal challenge in developing predictive relationships between exposure and efficacy. Many factors impact penetration into target tissues such as protein binding, selective barriers, and uptake or efflux transporters at the blood-tissue barrier. Furthermore, even when tissue disposition is achieved activity may be related to unbound fractions in the tissue rather than the total tissue concentration.

A thorough understanding of these disposition challenges is required to guide lead optimization, predict in vivo activity in animal models, and to identify any species-dependent variables that may impact the likely human clinical dose.

In this webinar we will discuss:

• A tissue disposition-driven rationale to support lead optimization.
• The bioanalytical strategy employed for high efficiency tissue analysis.
• For an anti-infective, use of in vitro time-kill and reversibility kinetics to correlate exposure (based on unbound concentrations in tissue) to pharmacodynamic measures that best predict efficacy.
• Compound modification and pro-drugging strategies for targeted tissue disposition, and rejuvenation of intellectual property.

Speakers

Steve Wring, Ph.D., Director of Drug Metabolism and Pharmacokinetics, SCYNEXIS, Inc.

Dr. Steve Wring is the Director of Drug Metabolism and Pharmacokinetics for SCYNEXIS, Inc., with responsibility for advancing new drug-like molecules from early hits through lead optimization to candidate selection for human and animal health indications. Recently, he has focused on programs to improve drug disposition for skin targets, and anti-infective neglected disease research including human African trypanosomiasis and visceral leishmaniasis programs. Prior to joining SCYNEXIS in 2007, Dr. Wring was Principal Investigator of DMPK at Trimeris Inc., where he led the DMPK optimization of synthetic peptide and small molecule fusion inhibitors of HIV infection. Before joining Trimeris in 2002, he gained 11 years discovery and development experience with GSK, both in the UK and USA.

Dr. Wring received his PhD in Analytical Chemistry from the University of the West of England (Bristol, England) and has professional qualifications in Clinical Biochemistry and an MSc in Instrumental Analysis.

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Tom von Geldern, Ph.D., Pharma/Biotech Consultant, Embedded Consulting

Tom von Geldern has been an independent consultant to the Pharmaceutical and biotech industries since 2007, specializing in medicinal chemistry and discovery strategy and tactics. Prior to this, Dr. von Geldern spent over 20 years in the Pharmaceutical industry, most recently serving as a Research Fellow and Senior Group Leader at Abbott Laboratories. In this capacity he led medicinal chemistry efforts resulting in the identification of clinical candidates in the areas of oncology, inflammation, cardiovascular and metabolic diseases. He is an author of more than 80 peer-reviewed articles, an inventor on 52 US patent applications, and has lectured by invitation on more than 50 occasions.

Dr. von Geldern received S.B. degrees in Chemistry, Mathematics, and Biology from MIT, a Ph.D. in Chemistry from the University of California at Berkeley, and performed post-doctoral research at Stanford University.

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