WASHINGTON and INDIANAPOLIS, April 4 /PRNewswire/ -- Semafore Pharmaceuticals, Inc., an emerging leader in small molecule cancer therapeutics addressing critical cell signaling pathways, today announced that preclinical data presented at the 97th Annual Meeting of the American Association for Cancer Research (AACR) further support advancement of Semafore’s PI3 Kinase inhibitor SF1126 into clinical trials.
The first set of data, produced through the collaborative efforts of researchers at The University of Texas M. D. Anderson Cancer Center and Semafore, demonstrate SF1126 selectively inhibits intracellular PI3K signaling pathways and PI3K-dependent cancer related biological functions. Data are also presented using the non-invasive technology of FDG-PET imaging to monitor effects at the tumor site. The studies have further identified potential molecular markers, and have shown that cancer cells with a mutation causing activation of the PI3K pathway are more sensitive to SF1126 treatment. These data will help guide selection of patients likely to respond to specific therapies targeting the PI3K pathway.
“Using in vitro and in vivo models of ovarian and breast cancers, we confirmed the mechanism of action of SF1126 by demonstrating PI3K inhibition through measurement of multiple downstream markers,” said Gordon. B. Mills, M.D., Ph.D., chairman, Department of Molecular Therapeutics, M.D. Anderson Cancer Center. “Semafore is also using data from our novel PET imaging studies for the investigational new drug application that Semafore is preparing for SF1126. They intend to monitor and use these PET images as biomarkers of activity and secondary endpoints in Semafore’s early clinical programs.”
The new study data validate previous studies with SF1126, which showed decreased tumor growth and prolonged survival in mice with PTEN mutant xerographs and other potential molecular markers for selection of patients likely to respond. The new data also demonstrate that tumors treated with SF1126 show significantly less glucose uptake than either normal tissue or tumors treated with Taxol(R) (paclitaxel).
The glucose uptake, which can be monitored by F18-labeled FDG-PET scanning, is an important measure of anti-tumor activity of SF1126. This is particularly relevant as Semafore prepares to move into clinical studies. It also directly supports the new Oncology Biomarker Qualification Initiative (OBQI), a joint agreement recently announced by the U.S. Food and Drug Administration, the National Cancer Institute and the Centers for Medicare & Medicaid Services to collaborate on improving the development of cancer therapies through biomarker development and evaluation. The first focus of the group is to validate PET imaging in cancer clinical trials.
The second poster, authored by Donald L. Durden, M.D., Ph.D., of Emory University* and Joseph Garlich, Ph.D., president of Semafore, and others, provides additional evidence that SF1126 can be selectively targeted to tumors through binding to specific integrins, cell surface receptors involved with tumor neovascularization. Data are also presented that demonstrate that administration of SF1126 results in increased uptake in the tumor of the active PI3K inhibitor -- by as much as two-fold greater than with the untargeted molecule -- and it also produces 10 times more of the inhibitor in the tumor than in plasma. These data provide further support that SF1126 is able to target significantly more PI3K inhibitor to the tumor while providing less exposure to healthy cells.
Dr. Durden commented, “The ability of the targeted prodrug SF1126 to deliver this high level of PI3K inhibitor uptake to the tumor is a novel and important observation. SF1126 is designed to target the tumor, where at physiological pH, the prodrug is converted to the active PI3K inhibiting drug. This targeting and conversion allows enough time for the prodrug to flood the integrin receptors at the tumor and subsequently release the PI3K inhibitor. We believe this is a key factor enabling us to target the central PI3K pathway and selectively prevent tumor growth without causing major systemic side effects.”
Dr. Durden was among the first to discover the role of PI3K/PTEN in tumor angiogenesis, which is the foundation of Semafore’s drug discovery and development programs.
The posters discussed in this press release include:
Identification of molecular markers for selection of patients likely to respond and pharmacodynamic markers of delivery of biologically relevant dose and early response in a novel phosphatidylinositol 3-kinase PI3K inhibitory prodrug, SF 1126, (Yiling Lu and Gordon Mills, et. al.) Late-Breaking Poster Session 2
Tuesday, April 4, 2006: 1:00 - 5:00 PM, Abstract Number: LB-274.
In vitro and in vivo preclinical studies on the novel PI3 kinase inhibitor SF 1126, (Garlich and Durden, et. al.) Late-Breaking Poster Session 2, Tuesday, April 4, 2006: 1:00-5:00 PM, Abstract Number: LB-275.
* AFLAC Cancer Center & Blood Disorders Service of the Children’s Healthcare of Atlanta and Emory University.
About Semafore
Semafore is an Indianapolis-based drug discovery and development company focused on small molecule modulators of the PI3 Kinase (PI3K) and PTEN cell signaling pathway, one of the most promising target pathways for multiple disorders, including the company’s focus--cancer. Semafore is one of the first biopharmaceutical companies to focus on PI3K and PTEN and has successfully discovered and is developing a portfolio of drug candidates. These programs have the potential to be the first of a new class of targeted cancer agents. The company’s lead clinical candidate, SF1126, is a pan-PI3K inhibitor and the company expects to file an IND for SF1126 in 2006 focusing on cancers known to be dependant on the PI3K pathway, such as brain cancer, Herceptin(R)-resistant breast cancer, hormone refractory prostate cancer and ovarian cancers. Semafore has also discovered the first drug-like small molecule PTEN inhibitors for cell protection, therapeutic angiogenesis and cancer sensitization. These compounds have exciting potential to completely change the way cancer and other disorders are treated. For more information see the company’s website at www.semaforepharma.com.
Contacts: Semafore Pharmaceuticals, Inc. Media: Derek A. Small Barbara Lindheim Director of Corporate Development GendeLLindheim BioCom Partners (317) 876-3075 (212) 918-4650
Semafore Pharmaceuticals, Inc.
CONTACT: Derek A. Small, Director of Corporate Development, for SemaforePharmaceuticals, Inc., +1-317-876-3075; or Barbara Lindheim, GendeLLindheimBioCom Partners, +1-212-918-4650
Web site: http://www.semaforepharma.com/
