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Semafore awarded patent covering PI3K prodrug technology targeting central cell signaling pathway.

Semafore Pharmaceuticals, Inc. (Indianapolis, IN), an emerging leader in small molecule cancer therapies addressing critical cell signaling pathways, announced that the United States Patent and Trademark Office has issued PI-3 kinase inhibitor prodrugs, United States Patent No. 6,949,537. This patent covers Semafore's lead clinical candidate, SF1126, and other prodrug compositions of the widely studied PI3K inhibitor, LY294002, that Semafore is evaluating as a novel therapy for cancer and other diseases. The PI3K pathway is a critical intercept point at the center of the mammalian cell signaling system, controlling multiple functions that contribute to the development and spread of cancer, including angiogenesis, apoptosis, migration, invasion and metastasis, and is mutated in cancer more frequently than any other cell signaling pathway.

"The claims awarded in this patent reflect the highly innovative nature of the targeted prodrug technology embodied in Semafore's lead compound," said Ronald Henriksen, chief executive office of Semafore. "This patent provides strong proprietary protection for SF1126, a PI3K inhibitor which is targeted to the rapidly growing new blood vessels associated with solid tumors, as well as for other prodrug compounds with different targeting agents. It gives us a solid proprietary foundation to support advancing SF1126 into clinical trials next year and to continue pursuing additional prodrug applications of our PI3K inhibitors."

PI3K is a high profile anti-cancer target because it controls multiple key cellular functions associated with cancer progression. The pathway's multi-tasking effect minimizes the possibility that alternative pathways will be able to stimulate malignant cell growth when the PI3K pathway is blocked by inhibitors. The fact that PI3K is also the key node in the activation of the pathway further limits the likelihood that it can be bypassed by other signaling mechanisms. But the centrality of the PI3K pathway also carries the risk of potential toxicity to other tissues. Semafore's prodrug technology offers a way to enhance delivery of PI3K inhibitors selectively to the tissues of therapeutic interest while lessening the systemic exposure seen with non-prodrug approaches.

"Researchers have long recognized the promise of the PI3K pathway as a target for new approaches to combating cancer, but the potential toxicity of the approach has been a concern and until now no pharmacologically applicable drugs have been available," said Gordon Mills, M.D., Ph.D., scientific advisor to Semafore and chairman, Department of Molecular Therapeutics at MD Anderson Cancer Center. "This is why we are so encouraged that Semafore's prodrug approach shows promise in overcoming these obstacles. Data from a growing number of preclinical studies demonstrate that SF 1126 achieves a ten-fold greater therapeutic index compared to an untargeted PI3K inhibitor, with no obvious toxicity. We look forward to continuing to work with Semafore to assess the anti-cancer potential of SF 1126 in human clinical trials."

Separately, Semafore disclosed additional promising preclinical data for SF1126. Dr. Donald Durden, who first discovered the importance of the PI3K pathway in promoting tumor angiogenesis and who is a founding scientific advisor to Semafore, presented data on SF1126 at Cambridge Health Institute's Targeted Cancer Therapies Conference on September 20, 2005 and at the Fourth International Congress on Targeted Therapies in Cancer, August 26-28, 2005. He described SF1126's anti-tumor and anti-angiogenic activity in vivo and its demonstrated efficacy without toxicity in multiple tumor xenograft models. Dr. Durden presented data from multiple studies confirming that Semafore's prodrug technology contributes to the increased efficacy and lack of toxicity of SF1126. He also highlighted the favorable pharmacokinetic (PK) and tumor pharmacodynamic (PD) characteristics of the compound.

"The PK/PD profile shown thus far for SF1126 demonstrates sustained levels of PI3K inhibitor in the blood and the tumor, which correlates with the knockdown of key molecular markers such as phosphorylated Akt and other downstream markers," said Dr. Durden. "This confirms that SF1126 is indeed knocking down PI3K in the tumor for prolonged periods -- which is precisely what we want to see going into human clinical trials."

Dr. Mills noted, "Furthermore, we hope to use the changes in downstream markers as biomarkers to provide us with a method to determine whether the appropriate dose of drug is being delivered to the tumor, helping us to establish optimal dosing levels in the upcoming clinical trials." Semafore, along with several of its collaborators, has been invited to present SF 1126 preclinical prostate cancer data at the 12th Annual Prostate Cancer Foundation Scientific Retreat later this month.

Semafore is a 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 in for SF 1126 in 2006 focusing on cancers known to be dependant on the PI3K pathway such as brain cancer, Herceptin-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.

Semafore Pharmaceuticals, Inc.

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Publication:BIOTECH Patent News
Date:Sep 1, 2005
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