VioQuest Pharmaceuticals' Novel Akt Inhibitor VQD-002 is Synergistic with Various Cancer Therapies in Preclinical Studies
VQD-002 (triciribine phosphate monohydrate, or TCN-P, also referred to as API-2) is a small molecule anticancer compound that inhibits activation of protein kinase B (PKB or AKT), a key component of the phosphoinosotide-3 kinase (PI3K) signaling pathway known to promote cancer cell growth and survival as well as resistance to chemotherapy and radiotherapy. VQD-002 has demonstrated anti-tumor activity against a wide spectrum of cancers in preclinical and clinical studies.
Findings presented at AACR include data from four studies conducted by independent researchers:
-- When combined with the ErbB2-targeting antibody trastuzumab, VQD-002 enhanced apoptosis both in vitro and in vivo in PTEN-deficient breast cancer models. Results of the study demonstrate that combining trastuzumab with inhibitors of the PI3K/Akt/mTOR pathway is a clinically applicable strategy for rescue of trastuzumab resistance caused by PTEN loss.
-- VQD-002 combined with dasatinib, a small-molecule inhibitor of multiple tyrosine kinases, enhanced apoptosis in various cell lines representing different types of sarcomas, including Ewing's, leiomyo-, lipo- and fibrosarcomas. Results of the study, funded by the Pediatric Cancer Foundation, indicate that the combination of VQD-002 and dasatinib may be an effective treatment regimen for sarcoma patients.
-- In a third study, inhibition of the Akt pathway following the introduction of VQD-002 was shown to sharply reduce miR-214-induced ovarian cancer cell survival. A specific form of microRNA, miR-214 induces cancer cell survival and cisplatin resistance through activation of the Akt pathway, an important regulator of cell proliferation and survival. These findings indicate that VQD-002 could play a role in reversing drug resistance in ovarian cancer for patients treated with cisplatin, which is used to treat a range of cancers including ovarian cancer.
-- In a fourth study, VQD-002 was combined with PD0325901, a MET tyrosine kinase inhibitor being developed by Pfizer, Inc. It has been demonstrated that MET, epidermal growth factor (EGFR) and HER-3 activate common downstream signaling pathways, such as PI3K, MEK, and MAPK. Results of the study demonstrate that VQD-002 was synergistic with PD0325901 in overcoming the effects of MET inhibition in cancer cells co-expressing EGFR and HER-3.
VQD-002 was also highlighted in an oral presentation during the "Targeting AKT in Cancer: Promise, Progress, and Potential Pitfalls (Basic Science-Clinical Interface Sessions: Pathways to Progress)" symposium. During the presentation, Phillip A. Dennis, M.D., Ph.D., of the Medical Oncology Branch of the National Cancer Institute's Center for Cancer Research, described VQD-002 as a bona fide Akt-inhibitor and discussed plans to study VQD-002 in combination with erlotinib (Tarceva(R); OSI Pharmaceuticals, Genentech, Roche), an epidermal growth factor receptor (EGFR) inhibitor. VioQuest Pharmaceuticals and the U.S. National Cancer Institute (NCI) Center for Cancer Research have entered into a Clinical Trial Agreement (CTA) to sponsor a clinical trial of VQD-002 in combination with erlotinib.
"Research has shown conclusively that VQD-002 inhibits activation of the Akt pathway. The results of these multiple preclinical studies indicate that VQD-002 might be effective in combination with drugs that have different mechanisms of action, such as trastuzumab, dasatinib, cisplatin, and other promising cancer therapies," commented Michael D. Becker, President and Chief Executive Officer. "Following completion of our dose-escalation trials for VQD-002 in both solid tumors and hematological malignancies, we will be positioned to evaluate this product candidate in combination therapy with a range of approved drugs."
A webcast replay of Dr. Dennis' presentation and abstracts and information about the AACR and its Annual Meeting can be found at www.aacr.org.
About VioQuest Pharmaceuticals
VioQuest Pharmaceuticals is a New Jersey-based biotechnology company dedicated to becoming a recognized leader in the successful development of novel drug therapies targeting both the molecular basis of cancer and side effects of treatment. VioQuest's oncology portfolio includes: Xyfid(TM) (1% uracil topical), for the treatment and prevention of Hand-Foot Syndrome, a common side effect from certain chemotherapy treatments, and to treat dry skin conditions and manage the burning and itching associated with various dermatoses; VQD-002 (triciribine phosphate monohydrate), a targeted inhibitor of Akt activation; and Lenocta(TM) (sodium stibogluconate), an inhibitor of certain protein tyrosine phosphatases such as SHP-1, SHP-2, and PTP1B.
Further information about VioQuest can be found at www.vioquestpharm.com.
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 forward-looking statements concern the focus of management's time and resources, the timing, progress and results of the clinical development, regulatory processes, potential clinical trial initiations of VioQuest's product candidates, as well as the potential role these product candidates may play in the treatment of cancers. 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 current expectations, forecasts and assumptions that are subject to risks and uncertainties, which could cause actual outcomes and results to differ materially from these statements. These statements are subject to various risks and uncertainties and include VioQuest's need for additional capital to fund its clinical development programs, 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 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, 2007. VioQuest assumes no obligation and does not intend to update these forward-looking statements, except as required by law.
Posted: April 2008