EpiCept Corporation reported on new clinical advancements for Azixa (MPC-6827), a vascular disrupting agent licensed by the company to Myriad Genetics, Inc. as part of an exclusive, worldwide development and commercialization agreement.
Myriad announced that it has initiated a third phase II clinical trial for Azixa in patients with non-small-cell lung cancer that has spread to the brain. The trial is designed to assess Azixa's safety profile and the extent to which it can improve the overall survival of these patients. Two additional Phase II trials for Azixa are underway in primary brain cancer and melanoma that has spread to the brain.
"We are pleased at the clinical advancement Myriad has reported on Azixa, and view it as further evidence of the commercial potential of the compound," stated Jack Talley, president and chief executive officer. "We believe that the study of Azixa in this new indication affords EpiCept with an expanded opportunity to capitalize on the financial benefits associated with our agreement with Myriad, including milestone payments, sublicensing income and potentially future royalties if Azixa continues to progress successfully."
Myriad is responsible for the worldwide development and commercialization of Azixa and any drug candidate that is developed from the series of compounds licensed by EpiCept to Myriad in 2003. The agreement requires that Myriad make future licensing, research and milestone payments to EpiCept, as well as pay a portion of any sublicensing income and pay a royalty on product sales. EpiCept will earn a milestone payment upon the dosing of the first patient in a Phase II trial and another milestone upon the dosing of the first patient in a Phase III trial for any use of the drug.
Myriad also reported data from two completed Phase 1 clinical trials of Azixa in a total of 66 patients, one in patients with refractory solid tumours that may also have had brain metastases and the other in patients with known brain metastases. The trials were designed to explore the safety and pharmacokinetics of Azixa and to find the maximum tolerated dose of the compound. Myriad reported that in the Phase 1 studies, Azixa appeared to have a biological effect on patients' metastases from many different primary tumours, including non-small-cell lung cancer, which is consistent with the mechanism of the drug candidate.
Azixa is one of two compounds in clinical trials discovered through EpiCept's Anti-cancer Screening Apoptosis Program (ASAP). EPC2407, a novel small molecule vascular disruption agent and apoptosis inducer for the treatment of cancer patients with advanced, solid tumours and lymphomas, is currently in Phase I clinical development by EpiCept. In July 2007, EpiCept announced the acceleration of the Phase I clinical trial, with results expected later this year. EpiCept expects to initiate a second Phase I efficacy trial for EPC2407 as a combination therapy in patients with well vascularized solid tumours and intends to choose multiple tumour targets for the compound's phase II trials as the clinical profile from the ongoing monotherapy trial emerges.
Cancer 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.
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, as well as 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 tumour models and identified molecular targets.
EpiCept is focused on unmet needs in the treatment of pain and cancer. EpiCept has a staged portfolio of pharmaceutical product candidates with several pain therapies in late-stage clinical trials, and a lead oncology compound (for acute myeloid leukaemia, or AML) with demonstrated efficacy in a Phase III trial; a marketing authorization application for this compound has been submitted in Europe.