INDIANAPOLIS and BOSTON, June 9 /PRNewswire/ -- Semafore Pharmaceuticals, Inc., an emerging leader in developing small molecule cancer therapies addressing critical cell signaling pathways, today presented the first in vivo data showing that a PI3K inhibitor with proprietary targeting modifications can be effective and safe in a mouse model of non-small cell lung cancer. The data were presented by Jing Dong Su, M.D., Ph.D., Semafore Senior Research Scientist, at the Cambridge Healthtech Institute's Second Annual Conference on Protein Kinase Targets in Boston.
The PI3 kinase pathway is a controlling mechanism for multiple cellular functions. The importance of its role in tumor angiogenesis was discovered by Donald Durden, M.D., Ph.D., now Senior Scientific Advisor to Semafore. Because PI3K is associated with multiple cellular functions that can stimulate the growth of cancer cells, inhibiting it has great promise as a way to slow or stop tumor growth. Additionally, unlike most current treatments, inhibiting PI3K minimizes alternative pathways for malignant cell growth. However, this same broad range of activity also means that inhibition of PI3K systemically can potentially result in significant toxicity. The new data presented by Semafore demonstrate that inhibiting PI3K through use of a proprietary prodrug specifically targeted to tumor neovasculature can be both effective and have limited toxicity, even when dosing is substantially higher than the lethal dose of a non-targeted PI3K inhibitor.
"Demonstration of the ability to safely block PI3K is an important development because it is a non-redundant cell signaling pathway for tumor development -- that is, tumor growth is less likely to be stimulated through an alternative route," said Dr. Durden, now at Emory University School of Medicine. (1) "These encouraging findings suggest that it may well be possible to develop targeted PI3K inhibitors that offer superior efficacy and good safety in combating cancer."
The Semafore inhibitor, SF1126, is a prodrug with modifications designed to specifically target tumor neovascularization. The data presented at the CHI conference show SF1126, as a single agent, caused a 68 percent reduction in tumor volume with no significant weight loss (an indicator of toxicity) compared to 49 percent tumor reduction with significant weight loss for a non-targeted PI3K inhibitor. The study was conducted in a mouse model of non- small cell lung cancer using an aggressive cell line (H1299). Toxicity for SF1126 remained low even with a dose that was 37 percent higher than the fatal dose of the untargeted inhibitor.
"This is an important milestone for Semafore because it is the first demonstration in vivo of the anti-cancer therapeutic potential of our lead PI3K inhibitor," said Joseph Garlich, Ph.D., president and chief scientific officer of Semafore. "It confirms our ability to target the therapeutic effects of SF1126 to achieve encouraging efficacy results with good safety, providing the first demonstration that the powerful PI3K mechanism can be used as a practical and promising target for more effective cancer therapies."
Animal testing of SF1126 is continuing, and Semafore expects to file an IND and initiate clinical trials with the compound in the second half of next year.
(1) Professor of Pediatric Oncology and Hematology at Emory University School of Medicine, and Scientific Director of Basic and Translational Research at the AFLAC Cancer Center & Blood Disorders Service of the Children's Healthcare of Atlanta and Emory University. About Semafore
Semafore is an Indianapolis-based company discovering and developing small molecule cancer drugs to modulate critical cell signaling pathways. The company's programs leverage a breakthrough -- the discovery of the PI3K /PTEN pathway's role as the primary non-redundant controlling mechanism for angiogenesis, cell survival, programmed cell death (apoptosis), cell migration and cell proliferation. Semafore is establishing a leadership position in this important new area and has already produced a portfolio of high potential drug candidates. Its lead programs, Interceptors(TM) for cancer therapy and MarrowShield(TM) for protection by a single agent against radiation and chemotherapy-induced anemia, neutropenia, and thrombocytopenia, are in pre-clinical development and are scheduled to enter clinical trials in 2005. Semafore's lead products are expected to have significant efficacy advantages compared to existing and developmental cancer therapies. The company's core technology and intellectual property are exclusively licensed from Indiana University. For more information, see the company's Web site http://www.semaforepharma.com/ .
Contacts: Semafore Pharmaceuticals, Inc. Derek A. Small Director of Corporate Development (317) 876-3075 Media: Stephen Gendel GendeLLindheim BioCom Partners (212) 918-4650
Semafore Pharmaceuticals, Inc.CONTACT: Derek A. Small, Director of Corporate Development of SemaforePharmaceuticals, Inc., +1-317-876-3075; or Media - Stephen Gendel ofGendeLLindheim BioCom Partners, +1-212-918-4650, for Semafore Pharmaceuticals,Inc.
Web site: http://www.semaforepharma.com/