TCD announces first patient treated in its TCD-717 Phase I trial

www.tcdpharma.comFeb 28 2011

Traslational Cancer Drugs Pharma, S.L. (“TCD”) announced today that the first patient was treated on Friday the 18th of February with TCD-717 in a Phase I study performed in patients with advanced solid tumors. TCD-717 is a first-in-class, small molecule that precisely inhibits Choline Kinase Alpha, an enzyme heavily involved in the carcinogenic process. A total of 30 patients are planned to be treated in the trial, which will be conducted in accordance with FDA approval, in two leading medical centers in the U.S. The
Principal Investigators are Dr. Julie Brahmer at the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital in Baltimore; and Dr. Patricia LoRusso at the Barbara Ann Karmanos Cancer Institute in Detroit.

"The treatment of the first patient with TCD-717 represents a significant milestone for the Company. Our development team led by Dr. Beatriz Palacios worked tirelessly to transfer TCD-717 from the bench to the bedside" said TCD’s CEO, Ran Vigdor. "With TCD-717 we are implementing a novel strategy of utilizing phospholipid metabolism for the treatment of cancer. This first-in-class drug signals the adoption of a new treatment paradigm” added Pablo Cabello,  TCD’s President and Chairman of the  Board.

About the Trial

The trial is designed to primarily assess the safety and tolerability, pharmacokinetics and preliminary efficacy of TCD-717 given by intravenous infusion in patients with advanced solid tumors. Each patient will receive 2 weekly administrations of TCD-717 for a total of 6 cycles in the course of 28 days, unless disease progression or dose limiting toxicity occurs. Patients who do not have progressive disease after the last treatment will be offered to continue treatment. Patients will be enrolled in ascending dose cohorts of 3 patients and will be monitored for evidence of doselimiting toxicity. Once the maximum tolerated dose is reached, additional patients will be enrolled to confirm this dose.

See http://clinicaltrials.gov/ct2/show/NCT01215864?term=TCD&rank=2).

Choline Kinase Alpha (ChoKα)

Choline Kinase Alpha (ChoKα) is a key enzyme regulating the production of phosphatidylcholine, a critical structural component required for the formation of the cell’s membrane and cell proliferation. Due to this role, ChoKα belongs to a very unique type of molecules that are essential for the carcinogenic process.

TCD has demonstrated that the up-regulation of ChoKα is a critical element for the acquisition of the tumor phenotype and that this enzyme participates in at least three of the major steps in the generation of cancer: independent cell proliferation; evasion of apoptosis (cell death); and increased cell motility and metastasis.

ChoKα overexpression is an indicator of the more aggressive nature of the tumor. Thus, the use of ChoKα-inhibitors is expected to be effective in all tumor types including the more aggressive harder-to-treat cases. Lung cancer, breast cancer, colorectal cancer, ovarian cancer, prostate cancer and bladder cancer are just a few among the many cancer types characterized by ChoKα overexpression.

About TCD-717

TCD-717 is a first-in-class, small molecule that precisely inhibits ChoK. By inhibiting ChoKα TCD-717 destroys the cancer cells with minimal effects on normal cells. The difference in response to ChoKα inhibition between cancer cells and normal cells derives from the addiction of tumor cells to phosphatidylcholine. While ChoKα inhibition causes a temporary and reversible arrest of proliferation in normal cells, the tumor cells attempt to overcome ChoKα inhibition by activation of an alternative mechanism for generating phosphatidylcholine. This alternative mechanism enables the cell, to some extent, to continue the phosphatidylcholine production process, however it also leads to the production of Ceramides, a lethal metabolite that promotes apoptosis (programmed cell death) and causes the specific destruction of the cancer cell. It is this different response to ChoK inhibition between tumor cells and normal cells that makes TCD-717 a uniquely effective targeted treatment with an evident and overwhelming advantage over conventional, non-specific chemotherapy.