Plenary Speaker

The Challenge of Drug Discovery in the 21^st Century
Allen B. Reitz
USA


The discovery of new drugs to treat unmet medical need is a worthy and important human endeavor. New advances in our understanding of the molecular basis of disease have resulted in innovative small-molecule therapeutics that has revolutionized patient care for many indications. However, there has been an unexpected decrease in the productivity of biomedical research in the past decade, in which 30-50% fewer new molecular entities (NMEs) are being approved each year when compared to the rate of NME introduction in the 1990s. In 2008, only 21 NMEs were approved by the FDA even though spending on drug discovery research is now many times higher than in previous decades and important new enabling technologies have been developed and validated. This pipeline problem is associated with the difficulties of translating basic biochemical discoveries into preclinical development compounds suitable for entry into human clinical trials. These challenges are particularly severe for the infectious, neglected diseases that afflict one-sixth of humanity. An unexpected disconnect has developed, now often called the “valley of death”, between the translation of exciting new discoveries about the molecular basis of disease into preclinical development compounds suitable for acceptance into the costly and risky preclinical and clinical development programs required for human clinical use. Research tools such as high-content screening and fragment-based drug discovery have emerged in order to improve efficiencies in early drug discovery. In addition, in vitro drug suitability profiling via eADME profiling is now commonly integrated as early as possible into drug discovery programs to remove inappropriate chemotypes and individual compounds as early as possible. Innovation is now occurring more than ever before in smaller biotechnology companies and at the interface between private companies and academic or other public institutions. The Pennsylvania Center for Drug Discovery (PCDD) has recently been founded at the Pennsylvania Biotechnology Center (PBC) by PCDD directors Allen Reitz, PhD and Kathy Czupich, MBA, and is part of the Pennsylvania Commonwealth Institute. We have developed programs to advance the mission of accelerating the translation of new basic discoveries into therapies suitable for human clinical evaluation. The PCDD drug discovery capability is built upon a network of non-profit research institutions and small biotechnology companies using industry-standard metrics for the identification of hits, leads and preclinical development compounds, risk analysis and development. The PCDD is also meant to serve as a think tank to brainstorm ways to improve efficiencies and productivity in early drug discovery research, attracting top scientists from around the world. Jobs are already being created in the companies associated with the PCDD, helping to reintegrate biomedical scientists into the workforce who have been laid-off elsewhere. This lecture will highlight the challenges facing drug discovery research in the early part of the 21st Century, and focus on the relative merit of public private partnerships such as those fostered by the Pennsylvania Center for Drug Discovery with the goal of discovering new therapy for those with unmet medical need.