BASKING RIDGE, N.J., April 19, 2007 /PRNewswire-FirstCall/ -- VioQuest Pharmaceuticals, Inc. , a New Jersey-based biopharmaceutical company focused on acquiring, developing and commercializing targeted cancer compounds, announced data from its preclinical studies of VQD- 002, a direct inhibitor of Akt activation for the treatment of solid and hematologic tumors. Pre-clinical data was presented in a poster at the April 2007 Annual Meeting of the American Association for Cancer Research (AACR), held in Los Angeles, CA.
"We are very excited to see these findings presented at AACR for our direct Akt inhibitor, VQD-002, in combination with another targeted agent Cdk9. Given that VQD-002 has two Phase I/IIa monotherapy programs in solid and hematogical tumors; this compliments the body of evidence that strongly suggests that VQD-002 may work in combination with multiple agents. We are eager to use findings like this to help us design the undertaking of additional clinical trials in combination therapy in the second half of 2007. VQD-002 has also shown compelling preclinical activity in combination with other targeted therapies such as Herceptin (trastuzumab), and other tyrosine kinases used in the treatment in tumor types such as glioblastoma, lymphomas, refractory leukemias, breast, colon and non-small cell lung cancer," said Daniel Greenleaf, VioQuest's president and CEO.
"The pre-clinical data for VQD-002 presented at AACR showed that the compound, in combination with another targeted pathway inhibitor, roscovatine, repressed the growth of specific prostate cancer cells in vitro. This combination, which may inhibit the pathways of apoptosis (programmed cell death) and eventually have a clinical application in the treatment of prostatic cancer, was one of more than 400 publications provided at AACR, showing the importance of the Akt pathway in human cancer," said Dr. Edward Bradley, VioQuest's Chief S cientific Officer.
Information related to the presentations is as follows:
Abstract Number: 5399: Prostate cancer (PCa) is one of the most common malignancies in humans and the second leading cause of male cancer death in America. Prostate cancer mortality results from metastases to bones and lymph nodes and progression from androgen-dependent to androgen-independent disease. Therapeutics for these aggressive forms of cancers are lacking. Previously, we reported that the cyclin dependent kinase inhibitor (CDK) roscovitine down- regulates the expression of X-linked Inhibitor of Apoptosis (XIAP) in metastatic PCas and can induce cell death of PCas that express functional p53. In this study, we found that roscovitine can inhibit cell growth, reduce colony formation and induce apoptosis in PC3 and PC3-M cells that are p53 negative, when co-cultured with either LY294002 (LY) or Triciribine (also known as small molecular Akt/Protein Kinase B signaling Inhibitor-2 (API-2)), which are inhibitors of Akt. Neither roscovitine nor LY or API-2 by itself is sufficient to induce apoptosis of these tumor cells. Further, apoptosis induced by the combination treatment was inhibited by pre-treatment of PC3 cells with a pan-caspase inhibitor and caspase-3 and -9 inhibitors, but not a caspase-8 inhibitor, suggesting that the combination induce the mitochondrial pathway of apoptosis. However, the above combination treatment, when added to RWPE cells for 20 hours, had very little effect, suggesting that the combination treatment is not toxic to normal prostate epithelial cells. In PC3 cells, roscovitine reduced abundance of XIAP but not Mcl-1, whereas API-2 induced Bim. The effect of roscovitine was mimicked by depletion of Cdk9, but not Cdk7 by RNA interference. Moreover, depletion of XIAP or Cdk9 by RNA interference was sufficient to sensitize PC3 and PC-3M cells towards API-2 and induce apoptosis. Collectively, these studies suggest that combined inhibition of Cdk9 and Ak t can be effective in treating metastatic prostate cancer in the future.
Presentation Title: Combined inhibition of Cdk9 and AKT induces apoptosis of metastatic prostate cancer cells Author Block: Subhra Mohapatra, Baoky Chu, Xiuhua Zhao, Jin Cheng, W. Jackson Pledger. H. Lee Moffitt Cancer Ctr. & Res. Inst., Tampa, FL
About VioQuest Pharmaceuticals
VioQuest Pharmaceuticals, Inc. (http://www.vioquestpharm.com) focuses on acquiring, developing, and commercializing targeted late preclinical and early clinical stage therapies with unique mechanisms of action for oncology, viral and autoimmune disorders. VioQuest has two targeted therapeutics in Phase I/IIa clinic trials: VQD-002 which inhibits activation of Akt that is seen at abnormally high levels in breast, ovarian, colorectal, pancreatic, and hematologic tumors; and Lenocta (TM), an inhibitor of specific protein tyrosine phosphatases, which has shown compelling preclinical activity in both renal and melanoma cancers. In addition, VioQuest and the U.S. Army are planning to submit an NDA to the FDA in 2007 for Lenocta (TM) for the treatment of leishmaniasis. VioQuest also has recently in-licensed Xyfid (TM), a topical therapy which has shown early clinical promise in the treatment and prevention of chemo-induced hand-foot syndrome.
This press release contains forward-looking statements that involve risks and uncertainties that could cause VioQuest's actual results and experiences to differ materially from the anticipated results and expectations expressed in these forward-looking statements. These statements are often, but not always, made through the use of words or phrases such as anticipates, expects, plans, believes, intends, and similar words or phrases. These statements are based on cu rrent expectations, forecasts and assumptions that are subject to risks and uncertainties, which could cause actual outcomes and results to differ materially from these statements. Among other things, there can be no assurances that the FDA will approve VioQuest's planned NDA submission relating to Lenocta(TM) for the treatment of leishmaniasis, and even if approved, there is no assurance that VioQuest will be able to successfully commercialize Lenocta(TM) for the treatment of leishmaniasis or any other indication, or that VioQuest will receive any proceeds in connection with a sale or other disposition of its Chiral Quest division. Other risks and uncertainties include the possibility that the results of clinical trials will not support VioQuest's claims, the possibility that VioQuest's development efforts relating to its product candidates, including Lenocta(TM) and VQD-002, will not be successful, the inability to obtain regulatory approval of VioQuest's product candidates, VioQuest's reliance on third-party researchers to develop its product candidates, its lack of experience in developing and commercializing pharmaceutical products, and the possibility that its licenses to develop and commercialize its product candidates may be terminated. Additional risks are described in VioQuest's Annual Report on Form 10-KSB for the year ended December 31, 2006. VioQuest assumes no obligation and does not intend to update these forward-looking statements, except as required by law.
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