Semafore's SF1126, a Vascular Targeted Pan-PI3K/mTOR Inhibitor, Is Well Tolerated and Demonstrates Activity in Phase I Solid Tumor Patients

Clinical Data Presented at the 2009 ASCO Meeting

INDIANAPOLIS, May 30 /PRNewswire/ -- Semafore Pharmaceuticals, Inc., a privately held cancer drug discovery and development company, today presented data from a Phase I clinical trial of its vascular targeted pan-PI3K/mTORC1/2 inhibitor, SF1126, at the 2009 American Society of Clinical Oncology (ASCO) Annual Meeting, being held in Orlando, Florida.

Dr. E. Gabriela Chiorean, from the Indiana University Simon Cancer Center in Indianapolis, IN presented the interim Phase I data on SF1126 in 36 advanced solid tumor patients. The majority of patients were heavily pretreated with a median of four prior chemotherapy regimens. Sixteen of 36 (44%) patients achieved disease stabilization with a median duration of 12 weeks. Of note, a GIST, endometrial, and prostate cancer patient each achieved durable stable disease for 20 weeks (5 mos.). These specific tumor types are associated with aberrations of the PI3K pathway that commonly lead to resistance and poor prognostic outcomes.

Pharmacodynamic analysis of tumor tissue confirmed inhibition of the PI3K pathway by complete absence of a downstream target (pS6). In contrast, a normal tissue (skin) demonstrated no inhibition providing evidence of tumor selectivity of SF1126. Pharmacokinetics displayed dose proportionality and no accumulation between cycles.

SF1126 was well tolerated. The most common side effects were grade 1 or 2 vomiting (42%), nausea (39%), diarrhea (33%), fever (22%), fatigue (19%), chills (14%), and puritis (11%). There were two patients with grade 3 toxicity, one with diarrhea, the other with urticaria and pruritis. Notably, there were no clinically significant changes in glucose or insulin levels reported.

"Based on these Phase I results we are encouraged that SF1126 is well tolerated and may hold promise for the treatment of solid tumor malignancies," said Dr. Chiorean.

This multi-center Phase I study was conducted at: Indiana University Simon Cancer Center, Indianapolis, IN; Arizona Cancer Center, Tucson, AZ; Winship Cancer Institute, Emory University, Atlanta, GA; Scottsdale Clinical Research Institute, Scottsdale, AZ.

About SF1126

SF1126 is the only clinical stage vascular targeted pan-PI3K inhibitor that selectively inhibits all PI3K class I isoforms and other key members of the PI3K superfamily, including mTORC1/2, DNA-PK, PLK-1, CK2, ATM and PIM-1. SF1126 is designed to inhibit both angiogenesis and cell proliferation by targeting and binding to integrins that are expressed on the surface of new tumor vasculature and within the tumor compartment.

In preclinical xenograft models SF1126 has demonstrated broad activity as a single agent; synergy with commonly used chemotherapy agents, targeted agents, and radiation; and has been shown to reverse resistance mediated through the PI3K/PTEN pathway.

About PI3 Kinase

Phosphatidylinositol 3 kinases (PI3K) are involved in one of the major pathways of intracellular signal transduction and are important in controlling cell growth/angiogenesis, differentiation, proliferation and survival/apoptosis. Dysregulation of the PI3 kinase signaling cascades can lead to cancer and aberrant PI3K pathway activity is observed with high frequency in a variety of tumor types. PI3K signaling through its downstream effectors AKT and mTOR is also known to promote tumor cell survival, proliferation, and growth. Dysregulation of PI3K signaling is also thought to contribute resistance to a variety of anticancer therapies. Thus, PI3K is considered a high value target in treating cancer.

About Semafore Pharmaceuticals, Inc.

Semafore is a clinical stage drug discovery and development company focused on small molecule modulators of the PI3 kinase and PTEN cell signaling pathway, a promising target pathway for multiple disorders, including the company's focus - cancer. Semafore is a leader in the development of PI3K inhibitors and one of the first biopharmaceutical companies to focus on both PI3K and PTEN inhibitors. The Company has successfully discovered and is developing a portfolio of drug candidates addressing these targets. Semafore is also leveraging its experience in the PI3K arena to identify and design inhibitors that block multiple pathways. For more information visit the Company's web site at www.SemaforePharma.com.

SOURCE Semafore Pharmaceuticals, Inc.

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