By Karen Pihl-Carey

In its first drug development program to apply fatty acid vector technology to anticancer agents, Protarga Inc. entered into a research and development agreement with the National Cancer Institute (NCI).

The focus of the agreement will be to develop new drugs by attaching promising anticancer agents to natural fatty acids.

"The idea is for an enabling technology, to the extent that the NCI has a variety of compounds that work very well in the test tube, but are too toxic in human use," said Robert Dickey, vice president of finance and corporate development and chief financial officer at Protarga. "So by linking them to fatty acids, we hope to actually be able to make those drugs usable in humans."

Under terms of the agreement, the NCI will supply anticancer agents to Protarga. The company will chemically link them to fatty acid vectors. The NCI then will conduct preclinical studies of resulting compounds, identifying the best ones for clinical study. Protarga will hold the exclusive right to license patents resulting from the collaboration.

The Conshohocken, Pa.-based company was formed in 1992 with technology that came out of Harvard Medical School. At that time, it was called Neuromedica Inc. and it focused on neurology, using fatty acid vectors to deliver drugs into the brain.

About a year ago, the company began applying its Targaceutical technology to areas outside the brain. "So the company began applying that technology in a way that it would get something to the market in the fastest way possible," Dickey told BioWorld Today.

When the company's focus changed, the name changed - to Protarga, a name with a broader connotation and one that emphasizes the company's targeting technology.

About four years ago, the company began working on a compound that is now completing Phase I studies at Johns Hopkins Hospital. Taxoprexin docosahexaenoic acid-paclitaxel (DHA-paclitaxel) entered the clinic last year for cancer chemotherapy. Dickey expects it to move into Phase II trials later this year. It is a patented new drug developed by Protarga to treat solid tumors, and it is made by chemically linking paclitaxel, the active ingredient in Taxol, a taxane drug marketed by Bristol-Myers Squibb Co., of New York, to the fatty acid DHA.

DHA is a targeting vector meant to improve the pharmacological disposition of the compound. The novel mechanism of action may provide prolonged and higher concentrations of drug in tumor types that have not responded to previous taxane treatments. It also may provide better activity in current indications for approved taxanes.

In the agreement with NCI, Protarga intends to chemically link NCI's agents to natural fatty acids in order to deliver more of the agent to diseased tissue. This method creates what the company calls Targaceutical drugs, or small-molecule drugs with improved performance. NCI has more than 140,000 anticancer compounds, many of which kill tumor cells, but are too toxic to healthy tissues.

"We basically have laid down a path to take drugs from discovery to the clinic. And the NCI relationship is going to be looking at a variety of compounds, focusing on oncology and using the fatty acid vector technology to hopefully achieve the same things we've been seeing with this first compound," Dickey said.

Tumor cells accumulate fatty acids such as DHA to fuel their unregulated growth. Tumors obtain most of the fatty acids from the blood, and tumor growth is dependent upon an adequate supply. Protarga believes that fatty acid conjugates of cytotoxic antitumor drugs are accumulated by tumor cells through similar mechanisms as natural fatty acids. Targaceutical products also may increase the duration of drug action through sustained release in order to kill more slow-cycling tumor cells, the company said.

Protarga has a pipeline of Targaceutical products in development to treat certain cancers, neurological disorders and infectious diseases. It is developing a Targaceutical product based on clozapine therapy, which is marketed by Novartis AG, of Basel, Switzerland, as Clozaril, to treat psychosis. Clozaril's safety profile includes serious side effects affecting the heart and immune system. Clozaprexin DHA-clozapine, however, is designed to achieve bioequivalent levels of clozapine activity in the brain with substantially less free clozapine and its metabolites in the blood.

Protarga holds 11 U.S. patents covering Targaceutical products and technology. The company has been angel-financed, raising about $20 million since its inception, and it expects a Series D financing to be completed soon, Dickey said. Protarga may go public, he added, depending upon the success of its first product as it moves into Phase II trials.