HAMBURG, Germany - Eradicating the seeds of cancer relapse is the goal of the German firm Micromet GmbH. The Munich company develops new drugs against micrometastatic cells and has just been awarded a DM2.4 million grant from the German Ministry of Research and Technology (BMBF).

A clinical trial of Micromet's first lead molecule, an antibody-based compound, is expected to start by the end of this year.

Metastatic relapse is one of the major causes of mortality in cancer patients. In spite of very sensitive imaging and other diagnostic techniques for early detection of primary and secondary tumors, malignant cells may be shed at early tumor stages. They disseminate through the body and may lie dormant for many years, posing a lifelong threat of cancer relapse.

“These micrometastatic cells are single cells that spread from a tumor very early,“ Evelyn Wolf, biotechnologist at Micromet, told BioWorld International.

“For example, in bone marrow, frequently used as an indicator organ for dissemination, there may be one of them hiding among 2 million mononuclear cells,“ she said. “Applying standard methods with limited sensitivity, clinical researchers find such cells in 20 to 30 percent of breast cancer patients showing no metastasis yet.“

Micromet has developed concepts to search and destroy these micrometastatic cells. Single-chain antibodies have been made specific for both tumor-associated antigens and cytotoxic cells of the immune system.

Micromet Founder Involved In Panorex

“So these bispecific antibodies bind to the cancer cells and direct effector cells against them. Our technique enables us to design them tailor-made to target different types of tumors,“ Wolf added.

The concept is based on the work of Gert Riethmüller, director of the Institute for Immunology at Munich University and one of the founders of Micromet.

Several years ago, Riethmüller initiated a clinical trial using an antibody that had previously failed, when applied to late-stage cancer patients, to decrease their tumor load.

Instead, he administered the antibody to colorectal cancer patients who had had their primary tumor removed and showed no sign of metastasis. Riethmüller found these antibodies were efficacious in fighting minimal residual disease. Data from this clinical study showed a more than 30 percent reduction in mortality and led to the approval of the antibody, Panorex, for elimination of micrometastatic cells remaining after colon cancer surgery in Germany.

Panorex is made by Centocor Inc., of Malvern, Pa., and sold by Glaxo Wellcome plc, of London.

“So here we have not only a proof of concept, but a result which could only be reached by chemotherapy so far, a therapy putting a great strain on patients,“ Wolf said. “We are now working to improve the specificity and efficacy of our therapeutic molecules.“

Meanwhile, the company holds an intellectual property portfolio with several patent applications filed and exclusive licenses covering the detection and expansion of micrometastatic tumor cells and several bispecific and cell surface antibodies.

An extensive academic and clinical network consisting of the Institute of Immunology and the Institute for Human Genetics and Anthropology, both of Munich University, and the Central Hospital, of Augsburg, Germany, will aid the company to isolate and characterize micrometastatic cells, to establish detection systems and to identify potential targets. In addition, new compounds can be evaluated rapidly.

In a joint program with MorphoSys GmbH, of Munich, Micromet develops fusion proteins consisting of human antibodies joined with cytokines and other molecules known to stimulate the immune system.

Two of Micromet's bispecific antibodies directed against carcinoma cells and B cell tumors are due to enter Good Manufacturing Practices production later this year, a regulatory prerequisite for clinical trials. One of Micromet's proprietary therapeutic molecules will enter a clinical trial at the end of this year.

Founded in 1993, Micromet received DM5.25 million in a financing round led by Atlas Venture, of Amsterdam, the Netherlands, and supported by Technologiebeteiligungsgesellschaft tbg, of Bonn, and Bayern Kapital, of Munich, both federal and state funding instruments. Micromet has just started a second round of private placements with major venture capital companies.

Erich Felber, CEO of Micromet and formerly of Andersen Consulting, of Munich, and Schering-Plough Corp., of Madison, N.J., said, “We plan to expand rapidly. Both the second financing and the federal DM2.4 million grant we just received will help us to accelerate our research program.“

The staff of 23 will be expanded to 35 by the end of next year. An IPO is projected, Felber added, but is not expected before 2000. *