VioQuest Pharmaceuticals Presents Phase 1 Data Showing Promising Immune Response and Safety Profile of Lenocta
"To date, single-agent immune-based strategies have shown limited promise for treating well-established tumors or advanced cancer," said Michael D. Becker, president and chief executive officer of VioQuest Pharmaceuticals. "Based on clinical data demonstrating the safety and preliminary activity of Lenocta in combination with IFN alpha-2b and published preclinical data revealing the synergy between Lenocta and various cytokine therapies, we believe this novel combination may be a promising approach to immunotherapy for cancer patients."
Twenty-one patients with advanced solid tumors were enrolled in the study, including five patients with melanoma, four with pancreatic cancer, and three with colorectal cancer. The treatment cycle was six weeks in duration and used escalating doses of Lenocta (400 mg/m2, 600 mg/m2, 900 mg/m2, 1125 mg/m2, and 1350 mg/m2) administered daily on weeks one, two, four and five and a fixed dose of IFN alpha-2b (3 million units subcutaneously) administered on three days during weeks two, four and five. The primary objective of the Phase 1 dose escalation study was to determine the safety and tolerability of the combination regimen for patients with advanced solid tumors. As a secondary objective, the study also assessed immunologic efficacy.
Previously published preclinical studies demonstrated that Lenocta is a selective, small molecule inhibitor of certain protein tyrosine phosphatases (PTPs), such as SHP-1, SHP-2 and PTP1B, with demonstrated anti-tumor activity against a wide spectrum of cancers both alone and in combination with other approved immune activation agents including IL-2 and IFN alpha-2b. IFN alpha-2b is known to stimulate both dendritic cells and CD4+ T-cells, which can ultimately produce various factors such as perforin that can destroy tumor cells. However, the effect of IFN alpha-2b can be negated by SHP-1, which functions to "turn off" proteins downstream from the IFN alpha-2b stimulation. As a potent and selective inhibitor of SHP-1, Lenocta would be expected to restore or enhance response to IFN alpha-2b.
Results of the Phase 1 study demonstrate that Lenocta in combination with IFN alpha-2b was well tolerated at 900 mg/m2 in the regimen studied. Thirteen patients who received Lenocta at 900 mg/m2 or higher demonstrated increased adaptive and innate immune responses as evidenced by increased dendritic cells and CD4+ T-cells. The goal of the Phase 2a expansion of this study is to demonstrate clinical anti-cancer activity.
The abstract from the Lenocta study, entitled "Phase I dose-escalation study of sodium stibogluconate (SSG), a protein tyrosine phosphatase inhibitor, combined with interferon-alpha for patients with solid tumors" (abstract #3011), is available on the ASCO website at www.asco.org.
Lenocta (sodium stibogluconate) is a selective, small molecule inhibitor of certain protein tyrosine phosphatases (PTPs), such as SHP-1, SHP-2 and PTP1B, with demonstrated anti-tumor activity against a wide spectrum of cancers both alone and in combination with other approved immune activation agents, including IL-2 and interferons. PTPs are a family of proteins that regulate signal transduction pathways in cells and that have been implicated in a number of diseases including cancer, diabetes, and neurodegeneration. Lenocta is in a Phase 2a clinical trial as a potential treatment for melanoma, renal cell carcinoma, and other solid tumors.
In addition to its potential role as a cancer therapeutic, sodium stibogluconate has been approved in many countries around the world as a first-line treatment of leishmaniasis, an infection typically found in tropic and sub-tropic developing countries. Based on historical published data and a large observational study conducted by the U.S. Army, data from approximately 400 patients could be utilized to support a New Drug Application for Lenocta with the U.S. Food and Drug Administration (FDA) in 2008. Lenocta has been granted Orphan Drug status for leishmaniasis.
With regard to leishmaniasis, the recently enacted Food and Drug Administration Amendments Act of 2007 adds new Section 524 to the Federal Food, Drug and Cosmetic Act designed to encourage the development of treatments for tropical diseases. The new section establishes a program under which FDA will issue transferable vouchers that may be redeemed to obtain priority review of a future application upon approval of a product for the treatment of a tropical disease.
A priority review voucher will be awarded to a sponsor upon approval of a tropical disease product application. A tropical disease product application is a new chemical entity human drug application that is itself deemed eligible for priority review under the preexisting priority review criteria and is approved for use in the prevention, detection, or treatment of a tropical disease.
A priority review voucher may be redeemed for priority six month review of one new drug application submitted under Section 505(b)(1) of the FFDCA or one biologics license application submitted under Section 351 of the Public Health Services Act that would otherwise be reviewed under FDA's standard 10 month review clock.
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 timing, progress and results of the clinical development, regulatory processes, potential clinical trial initiations of VioQuest's product candidates, as well as our ability to complete strategic transactions. 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 immediate need for additional capital to cover its current obligations and future operating expenses and 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: June 2008