Semafore Pharmaceuticals Commences Phase I Expansion Study of Novel Dual PI3K-mTOR Inhibitor in B-Cell Malignancies
Supported by Encouraging Preclinical Results Presented at the AACR Annual Meeting
First Patient Dosed in Phase I Expansion Study Under New Agreement with Technomark Life Sciences
INDIANAPOLIS--(BUSINESS WIRE)--Apr 20, 2010 - Semafore Pharmaceuticals today announced the presentation of data demonstrating that SF1126, a novel small molecule inhibitor of phosphatidylinositol 3-kinase (PI3K) and mammalian target of rapamycin (mTOR), has broad preclinical anti-tumor activity in multiple myeloma and lymphoma. Data were presented in a poster presentation at the American Association for Cancer Research (AACR) Annual Meeting in Washington, D.C.
Late-Breaking Abstract No. LB-291 – “Translational studies of the dual mTOR-PI3K inhibitor SF1126”
Results of in vitro studies presented at AACR demonstrate broad anti-tumor activity with SF1126 across six lymphoma cell lines and support expanded Phase I clinical evaluation in patients with certain B-cell malignancies, such as such as indolent non-Hodgkin's lymphoma (NHL), chronic lymphocytic leukemia (CLL), and mantle cell lymphoma (MCL). Results of in vivo studies presented at AACR support combination trials with SF1126 and bortezomib in multiple myeloma. A copy of the abstract can be accessed through the AACR website, www.aacr.org.
“Independently published in vitro studies demonstrate that pan-PI3K inhibition has some desirable effects on chemotaxis and proliferation inhibition in CLL B-cells over delta isoform-selective PI3K inhibition, which provides a rationale to clinically explore the therapeutic activity of pan-PI3K inhibition with SF1126,” said Joseph Garlich, Ph.D., Semafore's Chief Scientific Officer. “Accordingly, we are exploring the therapeutic activity of SF1126 in CLL and other B-cell malignancies. The encouraging data presented at AACR provided additional support for the expansion of our Phase I clinical study into this disease setting and the first such patient was dosed earlier this month.”
Semafore Pharmaceuticals also announced today that the company has entered into an agreement with Technomark Life Sciences for the Phase I expansion of SF1126 in B-cell malignancies and ongoing clinical activities. Technomark's established product development and regulatory capabilities will help accelerate further clinical research with SF1126.
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.
SF1126 is the first small molecule dual PI3K-mTOR inhibitor in clinical development that is designed to overcome these concerns by incorporating a peptide inhibitor of Î±vÎ²3- and Î±vÎ²5-integrins, which are transmembrane cell adhesion proteins expressed in new tumor vasculature and within the tumor compartment. By targeting integrins, SF1126 is designed to deliver more active drug in the vicinity of the tumor with lower inhibition of PI3K in normal cells and tissue. SF1126 inhibits all four class I PI3K isoforms along with other cancer targets such as mTOR, DNA-PK, PIM1, and PLK1. In preclinical studies, SF1126 has shown attractive pharmacokinetic and pharmacodynamic properties and compelling efficacy in xenograft models, both as a single agent and in combination with other therapies.
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. One event of Grade 3 study drug-related dose-limiting toxicity (DLT) was reported in 1 of 3 patients at 180 mg/m2. That cohort was expanded and no further DLTs were observed. The most common treatment-related adverse events have been nausea, vomiting, diarrhea, fever, fatigue and chills.
About Technomark Life Sciences
Technomark Life Sciences is a specialty life sciences firm with a worldwide reputation for excellence spanning over two decades. With offices in Research Triangle Park (NC-USA), London (UK), Mumbai (India), and Nanjing (China), the Company specializes in co-funding product development. As a follow-on to its first venture capital fund in 2002, in 2009 Technomark began its co-development/cofounding business model and is actively seeking opportunities for investment. For more information please visit www.technomarkls.com.
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 is developing 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 see the company's web site at www.semaforepharma.com.
Michael D. Becker
Acting Chief Executive Officer, Semafore Pharmaceuticals
President and Chief Executive Officer, MD Becker Partners LLC
Technomark Life Sciences
Posted: April 2010