BioWorld International Correspondent

PharmaMar SA, the drug discovery and development arm of Spanish chemicals group Zeltia SA, eliminated 45 positions and cut its spending forecasts in order to conserve €100 million in cash, following the failure last year to get its lead drug, Yondelis, approved in the European Union for treating soft-tissue sarcoma (STS).

The Madrid-based company, which has built a pipeline of compounds derived from marine organisms, now plans to burn €43 million in 2004, 33 percent less than in 2003, and €45 million and €44 million in 2005 and 2006, respectively. It aims to launch Yondelis in its first cancer indication - either STS, endometrial or ovarian cancer - in 2006.

If it can meet its spending targets, it would not require additional investment, it said, although that is contingent on the company licensing out at least one of its development projects.

"We have forecasted income of around €60 million and we have today cash of [about €100 million]," company Chairman José Fern ndez told BioWorld International.

The €60 million would include gains from planned real estate disposals and from anticipated milestones arising from its agreement with the Ortho biotech arm of Johnson & Johnson, based in Malvern, Pa., which is developing Yondelis in the U.S. But part of it would be derived from a licensing deal involving one of its other development-stage compounds.

The most advanced of those is Aplidin, a broad-spectrum cancer agent designed to inhibit tumor growth by inducing a p53-independent apoptosis response and by blocking cell division. It also displays anti-angiogenesis properties through inhibiting the secretion of vascular endothelial growth factor. The compound, currently in Phase II trials for a range of indications, gained EU orphan drug status last year for treatment of acute lymphoblastic leukemia.

PharmaMar also has put Kahalalide F, currently undergoing a Phase II trial for treatment of liver cancer, on the auctioneer's block. The compound, isolated from the sea slug Elysia rufescens, is preferentially toxic for tumor cells and acts by altering the function of the lysosomal membrane.

One other molecule has reached the clinic: ES-285, derived from the edible Arctic clam Mactromeris polynyma, is in a Phase I trial for treatment of solid tumors. Also, the company disclosed last week that a new compound, PM-10450, should enter clinical trials within the next month. That compound, which has broad-spectrum activity, is a modified version of a bacterial molecule, Fern ndez said.

PharmaMar is scaling back its R&D and sales and marketing operations. It also is making savings by switching over to a synthetic production process for Yondelis. Until now, it had harvested the product directly from the sea squirt Ecteinascidia turbinata, an expensive process that required it to grow several hundred tons of the organism. The company actually is increasing its spending on clinical development and is hiring additional personnel in that area.