By Mary Welch

Rhone-Poulenc Rorer Gencell (RPR) entered into a $40 million collaboration with Endocyte Inc. to develop cancer treatments based on systemic delivery of gene therapy using Endocyte's vitamin-based vector technology.

The agreement provides Collegeville, Pa.-based RPR, a subsidiary of Paris-based Rhone-Poulenc SA, with an exclusive license under Endocyte's intellectual property relating to the use of folate (folic acid) receptors for the delivery of oncology gene therapy products.

"When you're doing gene therapy, it requires three components," said Ron Ellis, CEO of Endocyte, of West Lafayette, Ind. "You need the genes, which we don't have but [RPR] does. You need a container to hold the gene, like a liposome. We have some technology but not as extensive as [RPR's]. And you need the technology that will target the gene to the cancer cell and put it inside the cell. That's what we bring to the partnership."

The deal also provides RPR with a two-year option to expand the scope of the license to include Endocyte's remaining vitamin receptor patents. RPR has agreed to pay up to $40 million in fees for licensing, research and development, and milestones.

Endocyte has the exclusive worldwide license to Purdue University's patents on the use of vitamins for cellular targeting and uptake. Essentially, vitamins are used to carry any therapeutic molecule or gene into a cancer cell to "fool" it. The company likens this deceptive action to a Trojan horse.

Folate Is Collaboration's Initial Vitamin Vector

The first vitamin being employed under the RPR collaboration is folate (folic acid), which is a necessary nutrient for dividing cells. Cancer cells have an insatiable appetite for folic acid, and employ special receptors to increase vitamin uptake. Researchers at Purdue discovered that, by attaching otherwise non-absorbable anticancer agents to folic acid, they could get the agents into the cell through endocytosis, mediated by folate receptors. Once inside the cancer cell, the agent can attack it.

As many as 30 percent of all cancers are believed to overexpress the folate receptor.

"The presence of folate receptors, which are overexpressed in cancer cells but not found in significant quantities on normal cells, guarantees that our delivery system targets only cancer cells," Ellis said.

Endocyte's vitamin-based drug delivery system may be better than current drug delivery technologies based on monoclonal antibodies for several reasons, Ellis said. First, folate is smaller, allowing better tumor access, and it is less expensive. Since folate is a natural substance and produces no immune response by the body, it can be given many times, unlike the monoclonals.

A wide variety of therapeutic molecules - toxic proteins, antisense nucleic acids and imaging agents, as well as genes - can be attached to the vitamins. Endocyte is currently in Phase I/II trials using imaging agents for cancer diagnosis with vitamins.

Rhone-Poulenc SA's stock (NYSE:RP) closed Tuesday at $51, up $0.75. n