By Karen Pihl-Carey

Medarex Inc. partnered its two lead products with Scil Biomedicals GmbH, giving the Germany-based company certain development and marketing rights in Europe and the Near East.

The agreement gives Scil commercial rights to MDX-RA, which is in a Phase III trial to prevent secondary cataracts, and MDX-210, which is in a Phase II trial to treat HER-2 overexpressing tumors. The rights concerning MDX-210 cover all methods of drug treatment except for cellular therapy.

For the rights, Scil will pay Medarex $4 million in an up-front licensing fee, as well as up to $25 million in committed funding to further develop the two products. Medarex also will receive royalties on future sales.

"It's a great opportunity. The cost of development is going to be picked up by our partner. They're very experienced pharmaceutical executives," said Donald Drakeman, president and CEO of Medarex. "We've retained commercial rights in the U.S. and other important markets in the world. It's just the kind of partnership we want to have."

Princeton, N.J.-based Medarex will make certain milestone payments to Scil upon reaching clinical and regulatory goals. Drakeman said its too early to estimate when the company might reach the regulatory filing stage.

In paying for the development of the two products, Scil will cover 100 percent of the remaining costs of developing MDX-RA. For MDX-210, Medarex can elect to pay a portion of the development costs and retain its commercial rights in North America and other parts of the world or have Scil pay all costs up to $17 million, therefore granting Scil certain co-marketing and co-promotion rights in the U.S. Any costs in excess to the $17 million would be shared equally.

"We have a chance to make a decision as to whether we want to fund half of the costs or have them pay them all," Drakeman told BioWorld Today.

MDX-RA is a monoclonal antibody linked to ricin, a plant-derived toxin. It is delivered directly into the eye after primary cataract surgery, where it binds to and destroys lens epithelial cells, which can otherwise proliferate and lead to secondary cataracts. A year ago, Medarex suspended enrollment in the Phase III trial of MDX-RA when 13 of 565 patients experienced sight-limiting events during the study. The events, however, did not appear to be caused by the drug, as seven of the 13 patients affected were on placebo. (See BioWorld Today, Dec. 15, 1998, p. 1.)

"We discovered the source of the problem, which was in the buffer, the formulation," Drakeman said. "And we reformulated the product to eliminate the problem."

MDX-210 is a bispecific antibody. It consists of fragments of two monoclonal antibodies linked together and is designed to induce tumor death by simultaneously binding to the protein HER-2 on the surface of cancer cells and to a receptor on immune system killer cells, such as monocytes and other white blood cells. In Phase II trials of the drug in hormone-refractory prostate cancer patients, 89 percent of patients experienced a reduction in the rate of increase of prostate-specific antigen levels, and 65 percent experienced a reduction in PSA levels.

Medarex's licensing partner for MDX-210, Novartis AG, of Basel, Switzerland, decided to drop out of the collaboration in February. (See BioWorld Today, March 1, 1999, p. 1.)

Medarex has five other products in the clinic. MDX-447 is in Phase II for cancer tumors that express the epidermal growth factor receptor. MDX-22, which is used to purge leukemia cells from the bone marrow of acute myeloid leukemia patients who are undergoing a transplant of their own bone marrow, also is in Phase II. MDX-220, an anticancer bispecific for tumors that express the protein TAG-72, is in a Phase I trial. MDX-33 is in Phase II trials to treat autoimmune hematological disorders. And MDX-CD4 is in Phase I to treat rheumatoid arthritis.

Medarex also has its HuMAb-Mouse system for creating high-affinity antibodies. The company just collaborated in December with IDM, of Paris, on generating fully human antibodies using the technology.

And the company's preclinical product, MDX-44, a monoclonal antibody that targets immune cells responsible for certain skin disorders and inflammatory conditions, showed positive results in a study when all targeted cells were eliminated from inflammatory sites in mice treated with the product. Results of the study appear in this month's issue of Nature Biotechnology.

Medarex's stock (NASDAQ:MEDX) closed Tuesday at $33, down $1.50.