HAMBURG, Germany - Medigene AG signed a licensing and development deal worth up to $34 million with Frankfurt-based Aventis Pharma AG.

The companies will cooperate in the preclinical and Phase I/II clinical trials of a tumor vaccine to treat malignant melanoma. The vaccine approach has been developed by Medigene using recombinant adeno-associated viruses (rAAV).

Aventis, the pharmaceutical company of Aventis S.A., said Medigene's technology was a very innovative approach that complemented Aventis' existing oncology pipeline. Aventis will be responsible for GMP manufacturing and Phase III trials, registration and commercialization. Medigene will receive research and development funding, up-front fees and milestone payments resulting in a potential deal value of up to $34 million. In addition, Aventis will pay royalties on all sales.

While Aventis is granted an exclusive license to develop and commercialize the vaccine in 37 countries including the U.S., the European Union and Japan, Medigene receives promotion rights for a number of East European, South American, and Far and Middle East countries.

One of the key problems in many cancers is tolerance of the tumor cells to T lymphocytes, so many companies try to develop strategies using genetically modified tumor cells as a therapeutic vaccine to stimulate the immune system.

To transduce the isolated tumor cells, Martinsried-based Medigene uses a proprietary plasmid based on an adeno-associated virus (AAV), which infects non-replicating cells, does not cause vector-induced immune reactions and has never been linked to any human disease. The vector carries genes for two immunostimulatory molecules. Medigene said it has improved upon existing AAV-based gene transfer systems.

Within 72 hours after infection of the cells, high levels of expressed capsid proteins lead to an efficient packaging of biologically active rAAV vectors. The company said this procedure increases the titer of the vectors by a factor of more than 100. A proprietary purification system removes adenovirus and other pathogenic viruses and allows a recovery rate of close to 100 percent. The transduction efficiency is 80 percent to 100 percent, it said.

After irradiation, the modified tumor cells are reimplanted. In animal trials the vaccine generated a strong proliferative T-lymphocyte response.

"With this technology, we have overcome the key problem of immune tolerance in melanoma, which is a very severe and threatening cancer as it is resistant to radiotherapy and most types of chemotherapy," Peter Heinrich, CEO of Medigene, told BioWorld International. "Our animal studies have demonstrated that the system is efficient, safe and ready for autologous and allogeneic approaches. As our preparations are free from wild-type and helper viruses they are suited even for in vivo administration, [such as] in genetic therapy of Parkinson's disease and hemophilia." Clinical trials to compare the different treatment regimens in melanoma patients are expected to begin in the third quarter, he said.

"As we want to establish a broad product portfolio and have already four projects in later developmental stages, we chose to collaborate with a strong partner in this early phase project," Heinrich said. "So we share the risks and generate a cash flow."

The approach could be expanded soon to other tumor types, he said. "This collaboration provides us with an opportunity to validate our rAAV concept through a strong partner, and this is a considerable advantage for further partnerships and for an IPO."