EpiCept Corporation Announces Initiation Of Phase I Study of EPC2407 For The Treatment Of Cancer

TARRYTOWN, N.Y., Dec. 19 /PRNewswire-FirstCall/ -- EpiCept Corporation today announced that it has initiated a Phase I clinical study of EPC2407, a novel small molecule vascular disruption agent and apoptosis inducer for the treatment of patients with advanced solid tumors and lymphomas. EPC2407 is the first of a novel class of microtubulin inhibitors discovered by EpiCept. These compounds cause caspase activation, cell cycle arrest, and apoptotic death in cancer cells.

(Logo: http://www.newscom.com/cgi-bin/prnh/20020513/NYM112LOGO )

Pre-clinical studies show that the anti-tumor effects of EPC2407 result from dual mechanisms, a primary effect on disruption of tumor vascular endothelial cells leading to hypoxia and central tumor necrosis, as observed with other vascular disruption agents; and a second and more direct apoptotic effect as well.

The Phase I trial of EPC2407 is being conducted in two U.S. cancer centers and will administer increasing doses to small groups in approximately 30 patients with advanced stages of solid tumors. The primary objectives of the study are to determine the safe doses and blood concentrations of the drug (maximum tolerated dose and pharmacokinetics). The study will also characterize the pharmacodynamic effects on blood flow and identify early signs of anti-tumor response as measured by CT scans, MRI or PET, in these advanced cancer patients with well vascularized solid tumors. The trial is expected to last one year.

EPC2407 is intended for the treatment of advanced cancer patients with solid tumors that are well vascularized. These tumors include the frequently occurring cancers of the lung, gastrointestinal tract, ovaries, and breast. Despite encouraging progress in treating earlier stages of these diseases, these cancers continue to have high mortality rates in spite of some new classes of anti-tumor agents in recent years.

EPC2407, identified through EpiCept's proprietary apoptosis screening technology, has demonstrated potent anti-tumor activity in pre-clinical in vitro and in vivo studies. The molecule has been shown to induce tumor cell apoptosis and selectively inhibit growth of proliferating cell lines, including multi-drug resistant cell lines. Murine models of human tumor xenografts demonstrated EPC2407 inhibits growth of established tumors of a number of different cancer types. Two manuscripts on this compound were published in the November 2004 issue of Molecular Cancer Therapeutics.

"The advancement of EPC2407 into clinical trials represents a further validation of our proprietary apoptosis screening technology and another achievement of a key corporate milestone," stated Jack Talley, President and Chief Executive Officer. "EPC2407 is the second clinical cancer candidate discovered by EpiCept researchers using this apoptosis screening technology and we continue to seek other promising cancer compounds targeting markets of substantial size and large unmet medical needs. This is an exciting time for our oncology program. In addition to these promising early-stage candidates, we are also continuing to move forward with Ceplene(TM), our lead candidate for the maintenance of first remission in patients with Acute Myeloid Leukemia, which is undergoing regulatory review in Europe."

About EPC2407

The IND filing for EPC2407 is based on the compound's effectiveness in several pre-clinical animal models of cancer and its potent anti-tumor effects both in vitro and in vivo. Nanomolar concentrations of the molecule have been shown to induce tumor cell apoptosis and to selectively inhibit growth of proliferating cell lines, including multidrug-resistant cell lines. Murine models of human tumor xenografts demonstrated that EPC2407 inhibits growth of established tumors of a number of different cancer types. The safety profile of the compound in standard toxicology studies also supports its testing in human clinical trials.

About EpiCept's Apoptosis Screening Technology

Cancerous cells often exhibit unchecked growth caused by the disabling or absence of the natural process of programmed cell death, which is called apoptosis. Apoptosis is normally triggered to destroy a cell from within when it outlives its purpose or it is seriously damaged. One of the most promising approaches in the fight against cancer is to selectively induce apoptosis in cancer cells, thereby checking, and perhaps reversing, the improper cell growth.

EpiCept's proprietary apoptosis screening technology can efficiently identify new cancer drug candidates and molecular targets that selectively induce apoptosis in cancer cells through the use of chemical genetics and its proprietary live cell high-throughput caspase-3 screening technology.

Chemical genetics is a research approach investigating the effect of small molecule drug candidates on the cellular activity of a protein, enabling researchers to determine the protein's function. Using this approach with its proprietary caspase-3 screening technology, EpiCept researchers can focus their investigation on the cellular activity of small molecule drug candidates and their relationship to apoptosis. The focus on apoptosis is achieved by screening for the activity of caspase-3, an enzyme with an essential role in cleaving other important proteins necessary to cause cell death through apoptosis.

This combination of chemical genetics and caspase-3 screening technology allows EpiCept's researchers to discover and rapidly test the effect of small molecules on pathways and molecular targets crucial to apoptosis, and gain insights into their potential as new anticancer agents. This screening technology is particularly versatile and can be adapted for almost any cell type that can be cultured, and it can measure caspase activation inside multiple cell types (e.g., cancer cells, immune cells, or cell lines from different organ systems or genetically engineered cells). This allows researchers to find potential drug candidates that are selective for specific cancer types, which may help identify candidates that provide increased therapeutic benefit and reduced toxicity.

EpiCept has identified several families of compounds with potentially novel mechanisms that induce apoptosis in cancer cells. Several compounds from within these families have progressed to lead drug candidate status with proven pre-clinical efficacies in tumor models and identified molecular targets.

EpiCept continues to screen additional compounds with the intent of identifying new potential drug candidates while also advancing the lead candidates it has already identified.

About EpiCept Corporation

EpiCept is an emerging specialty pharmaceutical company focused on unmet needs in the treatment of pain and cancer. The Company has a staged portfolio of product candidates with several pain therapies in late-stage clinical trials, and a lead oncology compound (for acute myeloid leukemia, AML) with demonstrated efficacy in a Phase III trial; a marketing authorization application for this compound has been submitted in Europe. EpiCept is based in New York, and the Company's research and development team in San Diego is pursuing a drug discovery program focused on novel approaches to apoptosis.

Forward-Looking Statements

This news release and any oral statements made with respect to the information contained in this news release contain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements include statements which express plans, anticipation, intent, contingency, goals, targets, future development and are otherwise not statements of historical fact. These statements are based on the Company's current expectations and are subject to risks and uncertainties that could cause actual results or developments to be materially different from historical results or from any future results expressed or implied by such forward-looking statements. Factors that may cause actual results or developments to differ materially include: the risk that Ceplene will not receive regulatory approval or marketing authorization in the EU, the risk that our other product candidates that appeared promising in early research and clinical trials do not demonstrate safety and/or efficacy in larger-scale or later stage clinical trials, the risk that the Company will not obtain approval to market any of its product candidates, the risks associated with reliance on additional outside financing to meet its capital requirements, the risks associated with reliance on collaborative partners and others for further clinical trials, development, manufacturing and commercialization of our product candidates; the cost, delays and uncertainties associated with our scientific research, product development, clinical trials and regulatory approval process; our history of operating losses since our inception; competition; litigation; the potential delisting of our common stock by the NASDAQ Global Market; risks associated with the material weaknesses in our internal controls and the outcome of our SOX 404 audit; and risks associated with our ability to protect our intellectual property. These factors and other material risks are more fully discussed in the Company's periodic reports, including its reports on Forms 8-K, 10-Q and 10-K and other filings with the U.S. Securities and Exchange Commission. You are urged to carefully review and consider the disclosures found in the Company's filings, which are available at www.sec.gov or at www.epicept.com. You are cautioned not to place undue reliance on our forward-looking statements, any of which could turn out to be wrong due to inaccurate assumptions, unknown risks or uncertainties or other risk factors.

EPCT-GEN

CONTACT: Robert W. Cook of EpiCept Corporation, +1-914-606-3500,rcook@epicept.com; or Francesca T. DeVellis of Feinstein Kean Healthcare,+1-617-577-8110, francesca.devellis@fkhealth.com

Web site: http://www.epicept.com/