This issue’s featured innovator, Professor Karl Hostetler, is an outstanding representative of the group of physician/ scientist/entrepreneurs who continue their research work at the University, while maintaining successful relationships with industry. Karl Hostetler, M.D., is professor of medicine at the UCSD School of Medicine and director of the Endocrine and Metabolism Clinic at the Veterans Affairs San Diego Healthcare System (VASDHS). Dr. Hostetler leads the scientific and clinical aspects of his research, while being adept at business via pharmaceutical consulting and through new company formation. In addition to authoring numerous journal articles, and being a member of many professional societies, Dr. Hostetler is a co-inventor on 28 U.S. patents and multiple foreign patents and pending applications.

Dr. Hostetler’s current research focus is viral diseases and the design and synthesis of new drugs to treat them. His group is pursuing the design and testing of antiviral agents with increased oral availability. These compounds are being developed for the treatment of diseases, such as smallpox and HIV and, additionally, are highly active against HPV- positive cervical cancer cells. Dr. Hostetler’s technology has provided the foundation for Chimerix Inc., a start-up company that will continue the necessary development and testing to bring the novel drugs to market.

Chimerix (www.chimerix-inc.com) was founded by Dr. Hostetler in 2002, to develop orally available medicines from bioactive molecules and is headquartered in San Diego with drug development and regulatory affairs offices in North Carolina. Besides smallpox, Chimerix is also working on the discovery and development of oral drugs for the treatment of drug-resistant HIV infection and viral hepatitis.

In early 2003, Dr. Hostetler and his collaborators published research results showing that a single dose of the oral smallpox drug he had developed was effective in protecting against lethal cowpox virus infection in mice. The drug (octadecyloxyethyl-cidofovir) is an analog of a FDA-approved antiviral called cidofovir, which has been chemically modified using Dr. Hostetler’s proprietary technology. In September 2003, Chimerix received a $36 million National Institute of Allergy and Infectious Diseases (NIAID) grant for the development of an oral smallpox therapeutic. With this five-year NIAID grant, Chimerix is continuing the development of new compounds for the treatment of smallpox.

Why smallpox, since the disease was eradicated in the United States in 1972 when routine vaccination was halted? Prior to 2002, the U.S. government provided the smallpox vaccine only to a small group working with smallpox and similar viruses in a research setting. Recently, there has been a renewed interest in smallpox vaccination and new treatment options as the danger of intentional release of the smallpox virus by terrorist groups has increased.

New treatment options for smallpox are sorely needed since the current vaccination approach has many disadvantages. Dr. Hostetler’s work on oral antiviral drugs provides an alternative approach with the potential to develop a safer and more effective drug for the treatment of smallpox, especially for the approximately 40 million people in the U.S. who can not safely use the current vaccine.

Entering the business world and starting a new company is not new to Dr. Hostetler. He successfully founded two other companies besides Chimerix over the past two decades, qualifying him as a serial entrepreneur. In the 1980s he cofounded local biotechnology company Vical Inc. (www.vical.com), and, in the 1990s, Triangle Pharmaceuticals based in Durham, North Carolina. During his time with these businesses, Dr. Hostetler served as director and vice president for research in the early years of Vical and continued to consult on their scientific advisory board for a period thereafter. Vical, publicly traded on the NASDAQ Market, develops biopharma- ceutical products based on patented DNA delivery technologies for the prevention and treatment of cancer and infectious diseases. In 1995, Dr. Hostetler co-founded Triangle Pharmaceuticals to license and market novel antiviral and anticancer therapies. Triangle was subsequently acquired by Gilead Sciences in December 2002 for $464 million.

While Dr. Hostetler continues his innovative research at UCSD and the VA Hospital, Chimerix will advance the development of his compounds under its license agreement with the University. This symbiotic relationship allows university research discoveries to continue down the development pathway to commercial markets through technology transfer licensing. This is in keeping with the goals of university technology transfer, contributes to economic development, and strengthens university/industry relationships.