West Coast Editor
Less than a week after licensing several small-molecule, preclinical oncology compounds from major institutions, Tigris Pharmaceuticals Inc. picked up rights to another - this time a Phase I aminoflavone (AF) prodrug for cancer from the National Institutes of Health.
The NIH drug, AFP-464, is undergoing two Phase I studies in patients with solid tumors. Under the terms of the license, Tigris would provide development-based undisclosed milestone payments and royalties.
Preclinical work suggests AFP-464 is converted to metabolites that bind covalently to DNA, resulting in p53 activation and apoptosis. In the National Cancer Institute's 60-tumor cell line screen, AFP-464 has shown particular sensitivity in breast, ovarian, lung and renal tumor lines. In vivo, AFP-464 has proved its mettle in several xenograft studies in mice with renal and breast cancer.
The NIH's technology abstract said that AFP-464 "displays improved solubility in aqueous solutions over the parent compound AF and can be converted rapidly to AF in plasma."
Edmundo Muniz, president and CEO of Bonita Springs, Fla.-based Tigris, said the compound's "very unique mechanism of action" makes it a particularly good fit for oncology-focused Tigris, but he declined to provide details of the deal's history, noting that another deal is in the works with NCI.
A synthetic material that is related to compounds found in plants called flavonoids, aminoflavone began screening in 1996 by the NCI's Developmental Therapeutics Branch Screening Technologies Program, also known as DTP. By the following year, AF and its prodrug yielded encouraging data against several renal, breast and ovarian cancer cell lines, and the NCI particularly liked that the activity had no significant correlation with other anticancer agents.
Earlier this month, Tigris licensed exclusive, worldwide rights from the H. Lee Moffitt Cancer Center and Research Institute, Yale University and the University of South Florida Research Foundation to commercially develop several molecularly targeted therapies in cancer. The small molecules include GFB-204, a selective dual synthetic inhibitor of VEGF and PDGF, and GGTI-2418. Phase I trials are expected to start next year.
"At least one of them is an oral drug," Muniz said, adding that Tigris' management team is "always open to any strategic alliances that can either speed up the process or expand the breadth and depth of our clinical development." He added that he is "very confident [we can] fully fund a comprehensive clinical development strategy."
The company's lead product is A-007, an intravaginal gel for high-grade cervical intraepithelial neoplasia (precancerous lesions in the tissues), which started a Phase II trial in April in 250 patients. Results with the self-administered treatment are expected next year.
Founded about a year ago with Muniz - formerly vice president of oncology at Indianapolis-based Eli Lilly and Co. - as its first hire, Tigris recruited others from the world of big pharma, which Muniz predicted will become a "key element" of the firm's success.
"Sometimes, finding and building the right management team is harder than discovering and developing drugs," he said, and Tigris sought to build a "lean and mean" organization that could make decisions and implement them quickly.
Anne White, Tigris' chief operating officer, held the same position in global oncology for Lilly. Binh Nguyen, vice president of clinical development and regulatory affairs, was director of Lilly's oncology platform team and pharmacogenomic program.
"We know how to take a baby from the early stages all the way through registration, globally," he said.
Muniz couldn't specify how many more cancer drugs Tigris might license.
"That's exactly the question we're evaluating right now," he said. "We've had a lot of companies and research institutions approaching us, asking if we can take on other compounds."