PHILADELPHIA--(May 20, 2015)-- The Wistar Institute and London-based global charity Wellcome Trust announce that they have signed a follow-on funding agreement in support of ongoing research and development of a new class of drugs useful for treating cancers associated with Epstein-Barr virus (EBV). The Seeding Drug Discovery Award of up to $5.6 million, over the next three years, will support ongoing translational research in the laboratory of Paul M. Lieberman, Ph.D., Hilary Koprowski, M.D., Endowed Professor, Professor and Program Leader, Gene Expression and Regulation Program, and Director, Center for Chemical Biology and Translational Medicine at Wistar.
If successful, this novel therapeutic could be the first to treat EBV-related cancers by attacking the virus as it remains dormant in a patient's cells. It is estimated that EBV causes nearly 200,000 cases of cancer worldwide each year, including Hodgkin's lymphoma, non-Hodgkin's lymphoma, gastric carcinoma, and certain head and neck cancers.
The project was initially funded in 2011 as a three-year, multi-stage effort with ongoing financial support based on the achievement of defined research milestones. Since then, Wistar investigators and their drug development partners, the Fox Chase Chemical Diversity Center in Doylestown, Pennsylvania, and DavosPharma in Upper Saddle River, New Jersey, have developed lead candidate therapeutic molecules demonstrating proof of concept in animal models. With this renewed grant money, they will continue optimizing these leads for safety, potency and efficacy with an eye toward assembling an Investigational New Drug package for the Food and Drug Administration, which would permit testing of the therapeutic candidate in a Phase 1 clinical trial.
"On behalf of The Wistar Institute, I would like to thank the Wellcome Trust for its continuing support and significant contributions made to advancing our EBV targeted cancer therapeutic program," said Dario Altieri, M.D., Wistar's president and CEO, and Cancer Center director. "This effort reflects translational research at its finest by combining a visionary charitable foundation, a promising line of research, and a solid plan for transforming basic science into practical medicine."
Approximately 90 percent of adults in the U.S. have antibodies indicating a current or past infection with EBV. EBV, the first human DNA tumor virus discovered, can linger in the human body for decades before causing infected cells to become cancerous. With limited therapeutic options for these cancers, long-term prognosis is poor.
EBNA1, which stands for Epstein-Barr virus Nuclear Antigen-1, is the only viral protein expressed consistently in all EBV-related cancers and is essential for the virus to reproduce, making it a prime target for therapeutic intervention.
"EBNA1 acts as a 'safe house' that keeps the viral DNA protected and active in tumor cells," said Lieberman. "Inhibiting EBNA1, therefore, should eliminate the viral DNA and prevent the growth of EBV-associated cancer." Lieberman is encouraged that his lab's work may also have value against other chronic diseases associated with EBV, such as multiple sclerosis and infectious mononucleosis.
To develop an anti-EBV drug, researchers began a complex screening process to find a small molecule that could chemically bind to EBNA1 and inhibit its ability to function. They began with a library of small "fragment" compounds. Using atomic resolution structures of fragments with EBNA1, they were eventually able to "build out" the fragments into leading candidate molecules that selectively inhibit the growth of EBV-infected cells.
With funds and intellectual contributions provided by the Wellcome Trust, Wistar researchers, together with their drug development expert network, will further optimize their small molecule inhibitors, with the aim of developing at least one chemical compound into a viable drug candidate. This drug candidate could then be used in clinical trials designed to determine its safety and effectiveness in humans.
"This is an investment in drug discovery, enabling a small team of experts to do the type of translational research typically seen in large drug companies," said Troy Messick, Ph.D., Senior Staff Scientist in the Lieberman laboratory and co-leader on the project. "If successful with the translational research funded by the Wellcome Trust, the program will be in a position to attract a commercial partner to undertake further clinical development."
About the Wistar Institute: The Wistar Institute is an international leader in biomedical research with special expertise in cancer research and vaccine development. Founded in 1892 as the first independent nonprofit biomedical research institute in the country, Wistar has long held the prestigious Cancer Center designation from the National Cancer Institute. The Institute works actively to ensure that research advances move from the laboratory to the clinic as quickly as possible. Wistar Science Saves Lives. http://www.
About the Wellcome Trust: The Wellcome Trust is a global charitable foundation dedicated to improving health. The Trust provides more than $1.1 billion a year to support bright minds in science, the humanities and the social sciences, as well as education, public engagement and the application of research to medicine. http://www.