Context - Why Academic Drug Discovery?

Scientific progress in the biomedical sciences has accelerated enormously over the last 2-3 decades. The cellular signal transduction processes and biochemical pathways that enable life are increasingly understood at the molecular level and the aberrations that result in disease can be defined within this rational context. Additionally, with the sequencing of the human and other genomes, the identity of the cast in this drama of life is known with ever greater certainty. Technology to enable discovery of ligands for molecular targets has also advanced such that many complimentary approaches exist for creating small molecule tools to interrogate biological processes. However, even as basic science and technology seem poised to create a revolution in the availability of potent, selective and safe small molecule drugs, the pharmaceutical industry, where >90% of drugs have historically been discovered, is struggling for survival. While industry investment in R&D has grown exponentially, the return in terms of New Chemical Entities (NCEs) approved as medicines has stagnated and pricing pressures and litigation have further eroded profitability. These conditions have resulted in frequent mergers, reorganizations and reductions in scientific staff across the industry.  This is highly disruptive to drug discovery projects which must survive several generations of R&D management during their >10 year life span. Given the rate of organizational change in the industry, it is increasingly difficult for a research strategy to bear fruit before it is abandoned. Additionally, there is a growing trend for larger pharmaceutical companies to outsource and externalize the early phases of drug discovery via either active partnerships or opportunistic in-licensing of NCEs. In this context, there is a clear societal need for greater organizational diversity and innovation in how drugs are discovered in order for advances in biomedical research to result in new medicines. Exclusive (>90%) reliance on large pharmaceutical companies for drug discovery will not suffice.

UNC possesses the scientific and medical talent to contribute substantially to the discovery of small molecule drugs; however, each new insight into human biology with potential therapeutic relevance faces similar challenges in translation – the lack of an experienced and dedicated chemistry/biology team to drive projects from target identification through lead or candidate discovery. The CICBDD will fill a key gap in expertise and resources at UNC and enable translation of basic scientific discoveries into potential human therapeutics. Importantly, the research culture of the University is based upon fostering innovation and nurturing new ideas – qualities that are essential for improving the success of early discovery efforts.

In addition to the expertise in basic biological sciences present in Pharmacology, Biochemistry, the Cancer Center and the Medical School, the School of Pharmacy has several initiatives that will strongly synergize with the drug discovery focus of the CICBDD: The Center for Nanotechnology in Drug Delivery (CNDD), the Institute for Pharmacogenomics and Individualized Therapy (IPIT) and the National Institute of Mental Health Psychoactive Drug Screening program (NIMH-PDSP). State of the art drug delivery systems developed in the CNDD will permit rapid progression of small molecules into a broad and genetically characterized set of animal models, provided by the IPIT & the NIMH-PDSP, which will create an enormously powerful mechanism for rapid target validation & compound profiling. UNC’s strengths in transgenic and ‘knock-out’ technologies are globally recognized as reflected in the recent award of the Nobel prize in Medicine and the Center will take advantage of these capabilities. The co-location of these efforts will greatly enhance successful translation of projects through the discovery and early development stages.

Summary

The University is poised to complete the cycle from basic scientific research through translational drug discovery to clinical studies in patients. The scientific opportunities, the unmet needs in healthcare and the need to diversify approaches to drug discovery are compelling. With the creation of the Center for Integrative Chemical Biology and Drug Discovery and the other initiatives mentioned above, UNC is making a bold move which will establish it as a premiere institution for integrated healthcare, enhance the economic development of the State, and further develop the University’s capabilities to educate and train the scientists and leaders of the future.