INDIANAPOLIS, April 5, 2011 (GLOBE NEWSWIRE) -- Semafore Pharmaceuticals today announced encouraging preclinical results for its lead product candidate, SF1126, in certain B-cell malignancies. The data demonstrated that the therapeutic effects of SF1126 are superior to a delta isoform-selective PI3K inhibitor (CAL-101) both alone and in combination with rituximab in two diffuse large B-cell lymphoma (DLBCL) cell lines. These data, generated through a collaboration with Dr. Daruka Mahadevan of Arizona Cancer Center, were presented during a late-breaking poster session at the 102nd Annual Meeting of the American Association for Cancer Research (AACR) in Orlando, Florida.
SF1126 is a novel peptidic prodrug that converts to LY294002, one of the most widely studied small molecule inhibitors of multiple, cancer-specific kinase targets, including all Class I phosphatidylinositol 3-kinase (PI3K) isoforms, mammalian target of rapamycin (mTOR), Pim-1, DNA-activated protein kinase (DNA-PK), and polo-like kinase 1 (PLK1).
"With the recent availability of CAL-101, we sought to conduct the first head-to-head study of two unique, clinical stage PI3K inhibitors in certain B-cell malignancies, such as DLBCL," said Daruka Mahadevan, M.D. Ph.D., Director, Phase I Program, Arizona Cancer Center. "Based on promising clinical activity demonstrated to date with mTOR inhibitors in DLBCL, we hypothesized that dual PI3K/mTOR inhibition would be superior to inhibition of PI3K, or certain isoforms, alone. In addition, Pim-1 has become a target of interest in various malignancies, including DLBCL, and recent preclinical studies indicate synergy between pan-PI3K and Pim-1 inhibitors. This suggests that enhanced efficacy might be achieved with a single molecule that inhibits PI3K/mTOR and Pim-1. The encouraging data presented at AACR confirm our theory and provide additional support for the ongoing Phase I clinical of SF1126 in combination with rituximab in B-cell malignancies."
To date, nearly 50 patients with solid tumors or hematological malignancies have been treated with SF1126 in Phase I trials. Administration of SF1126 at doses ranging from 90 to 1,110 mg/m2 has been generally well tolerated with the most common treatment-related adverse events have been nausea, vomiting, diarrhea, fever, and fatigue. The clinical investigation of SF1126 alone and in combination with rituximab in certain B-cell malignancies, including DLBCL, indolent non-Hodgkin's lymphoma (NHL), chronic lymphocytic leukemia (CLL), and mantle cell lymphoma (MCL), is currently being conducted at the Arizona Cancer Center. In November 2010, the U.S. Food and Drug Administration granted orphan drug designation to Semafore's SF1126 product candidate for the treatment of CLL.
The late-breaking poster (abstract number LB-383) at AACR, "Translational studies of the novel prodrug PI3K/mTOR/PIM1 inhibitor SF1126 in DLBCL," is being presented in Exhibit Hall A4-C on Tuesday, April 5th, 2011, from 1:00 pm – 5:00 pm Eastern Time. For additional information, or to request an electronic copy of the poster, please visit the company's web site at www.semaforepharma.com.
About SF1126 and the PI3K Pathway
The phosphatidylinositol 3-kinase (PI3K) signaling pathway is vital to several essential biological processes, such as cell growth, survival, motility, and metabolism. PI3K is commonly altered in human cancers, making inhibition of the target attractive for cancer therapy. However, the role of PI3K in a wide range of normal biologic processes raises potential concerns about its inhibition in non-cancerous tissues.
As the only PI3K/mTOR inhibitor prodrug currently in development, Semafore's SF1126 product candidate is designed to overcome these concerns by accumulating preferentially in tumor tissue in an attempt to maximize efficacy and minimize toxicity. SF1126 is a peptidic prodrug that converts to LY294002, one of the most widely studied small molecule inhibitors of multiple, cancer-specific kinase targets, including all Class I PI3K isoforms, mTOR, Pim-1, DNA-PK, and PLK1 that historically suffered from poor solubility. LY294002 is conjugated to an Arg-Gly-Asp (RGD) peptide via a cleavable linker to form SF1126, which has improved properties for clinical use. As a prodrug with enhanced solubility and site selectivity due to targeting of RGD-recognizing integrin receptors, SF1126 opened up a new avenue for the clinical development of LY294002.
About Semafore Pharmaceuticals
Semafore Pharmaceuticals is a private, clinical-stage biotechnology company dedicated to the discovery and development of novel small molecule signal transduction inhibitors targeting the phosphoinositide-3-kinase (PI3K) pathway for the treatment of cancer and other serious diseases. In addition to SF1126, the Company's pipeline includes SF2626, a next-generation dual MEK/PI3K inhibitor that is designed to simultaneously inhibit an additional key pathway critical to cancer progression using a single molecule. For more information, visit the company's web site at www.semaforepharma.com.