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Semafore's PI3 Kinase Inhibitor SF1126 is a Vascular Targeted Conjugate in Phase I Clinical Trials in Solid Tumors and Multiple Myeloma

SAN DIEGO, April 14 /PRNewswire/ -- Semafore Pharmaceuticals Inc. announced today on the occasion of a poster presentation at the 2008 AACR Annual Meeting that its integrin-targeted PI3 kinase inhibitor, SF1126, was shown to cause significant tumor regression in combination with rapamycin in a renal cell carcinoma mouse model. The combination of SF1126 (20 mg/kg i.v., 3x/week) with rapamycin (1.5 mg/kg i.p., 3x/week) administered simultaneously showed a 54 percent regression of the tumor volume versus starting tumor volume. This efficacy was significantly better than treatment with either agent alone or where the two agents were administered sequentially.

Angiogenesis plays a major role in the progression of renal cell carcinoma, and SF1126 was shown to dose-dependently inhibit endothelial cell proliferation in an in vitro model, while the mTOR inhibitor rapamycin (sirolimus) had no significant effect. SF1126 also showed dose-dependent cell signal (pAkt) inhibition in both renal cell carcinoma cells and endothelial cells under stimulation conditions using the growth factors IGF, VEGF and Bv8.

"There is significant biological rationale for combining targeted therapeutic agents in oncology to improve efficacy," said Dr. Dennis McKeever, Semafore's Chief Executive Officer. "The combination of SF1126, our lead product candidate, with rapamycin exhibited synergistic anticancer effects, and this increased effect was optimal when the agents were administered in combination as opposed to sequentially. SF1126 is currently in Phase I clinical trials in both solid tumors and multiple myeloma."

About SF1126

SF1126 is a small molecule conjugate containing a pan-PI3K inhibitor that selectively inhibits all PI3K class I isoforms and other key members of the PI3K superfamily, including DNA-PK and mTOR. A major factor in tumor resistance to approved chemotherapy agents is thought to be the activation of the PI3K/PTEN pathway. As a result, it is thought that inhibiting this pathway via SF1126 could cause the resetting of sensitivity to approved agents and exhibit synergistic anticancer effects.

About Semafore

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 one of the first biopharmaceutical companies to focus on both PI3K and PTEN and has successfully discovered and is developing a portfolio of drug candidates addressing these targets. For more information see the company's Web site at


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