Toxicogenomics and Personalized Medicine: Minimizing Toxicity While Optimizing Treatment

Organizers: George Zavoico, Cantor Fitzgerald and Marla Weetall, PTC Therapeutics

The use of pharmacogenomics and toxicogenomics to guide treatment options has already changed medical practice in certain genetic disorders, cancer, infectious diseases and other therapeutic areas. This symposium will bring together experts in pharmacogenomics, toxicogenomics, and drug discovery and development to discuss current and emerging applications of personalized medicine and its possible impact on the pharmaceutical industry, drug development and regulation, and clinical practice.

Speakers:  John Davis, Pfizer Global Research; Barbara J. Evans, University of Houston Law Center; Carol Reed, Clinical Data, Inc.; Steve Shak, Genomic Health; Langdon Miller, PTC Therapeutics

Abstracts

Application of Toxicogenomics in Preclinical Safety Assessment: Pathway Analysis and Biomarker Identification.
John W. Davis II, Ph.D., Pfizer Global Research Development.

Drug development is a long, complex and expensive process. Typical development timelines are between 10 and 15 years with attrition rates that are often too high for companies to sustain productive pipelines. Investigational and discovery toxicology are extensions of the field of general toxicology, created to fulfill the growing need for generating higher throughput, integrative, and predictive toxicological information, in an effort to reduce attrition at later stages of drug development. These novel ideas have begun to be employed more frequently and it's widely anticipated that this will pave the way for future drug testing paradigms. One aspect of this paradigm is the field of predictive toxicogenomics and recent innovations have led to increased application of this technology in preclinical safety assessment. Researchers have proposed using gene expression as a predictor of target organ toxicity, for the identification of biomarkers and to understand mechanism(s) of toxicity. This lecture will overview these applications and discuss how biomarker identification and pathway analysis can be used to increase knowledge of mechanism(s) of toxicity and advance molecules through development.

Making Personalized Medicine Work:The Legal and Regulatory Paradigm Shift
Barbara J. Evans, PhD, University of Houston Law Center

Achieving the full therapeutic and financial promise of personalized medicine will require modernization of the mid-20th century legal and regulatory frameworks for medical products on which the United States and other industrial nations continue to rely. This process is already underway. This talk identifies key barriers to widespread clinical application of personalized medicine and what is being done—and what still needs to be done—to address them. Topics will include FDA's regulation of drugs and test products; developments affecting non-FDA-regulated testing services; state-law issues that affect whether physicians will embrace this technology; strategies for minimizing lawsuit risks related to personalized medicine; and unresolved problems in privacy and intellectual property law that may affect the progress of this promising technology. The talk will explain how members of the scientific and investment communities can play an active role in encouraging needed legal and regulatory change.

A Novel Therapy Targeting Nonsense-Mutation-Mediated Genetic Disorders
Langdon Miller, MD, PTC Therapeutics

A nonsense mutation is a single-point alteration in DNA that results in the inappropriate presence of a stop codon in the protein-coding region of the corresponding mRNA transcript. Such a stop codon causes premature cessation of mRNA translation, with protein truncation leading to loss of function and consequent disease. Nonsense mutations are responsible for approximately 5 to 15% of over 2000 monogenetic disorders. PTC124 is an orally bioavailable small molecule designed to induce ribosomes to selectively read through premature stop codons, producing full-length functional