ByLudger Wess

BioWorld International Correspondent

HAMBURG, Germany - With a new strategy, Wilex Biotechnologie GmbH, of Munich, Germany, is attempting to develop therapeutics to block tumor cell invasion and metastasis in patients afflicted with breast, ovarian and gastrointestinal cancers. Clinical trials are expected to start in 1999.

Wilex is a spin-off of a clinical research group of the Women's Clinic at Technische Universitdt M|nchen. The group, led by Henner Graeff, was established in 1991 and consists of clinical researchers and natural scientists, a concept that has received continuous support by various private and public funding institutions in Germany and the European Union.

Olaf G. Wilhelm, founder and CEO of Wilex, worked in Graeff's group, which concentrates on certain aspects of cancer metastasis. "Cancer cell proliferation does not by itself lead to metastasis," Wilhelm told BioWorld International. "Cancer cells tend to cross tissue boundaries by adhesion to and subsequent degradation of components of the cellular matrix. So, it has long been suspected that extracellular proteolytic enzymes are involved in cancer-cell invasion and subsequent metastasis, as they are digesting the extracellular matrix of the surrounding tissue."

In the late 1980s Graeff and his co-workers, then working in Fritz Jaenicke's research group in Hamburg, discovered that high levels of a certain proteinase system - both the urokinase-type plasminogen activator uPA and its related inhibitor - were strong prognostic markers for increased tumor progression, a finding that "nobody was going to believe," Wilhelm said.

Now, however, the finding "is widely accepted, even by the FDA, and currently a multicenter study is being conducted in Europe to investigate the prognostic value further. In addition, many model systems have provided evidence that uPA indeed plays a causal role in cancer metastasis."

Working with a network of several clinics and research institutes in Munich, Graeff's group tried to elucidate the mechanisms of the uPA system and to develop strategies to block uPA and its inhibitor.

"The incentive to start Wilex came in 1996, with the first Business Plan Competition led by the business consultant firm McKinsey & Co.," Wilhelm said. "Fortunately, we won the first prize, worth DM30,000 [US$18,000], and were able to profit from a network of really helpful advisors, venture capital experts, etc., so that Wilex could be founded in October 1997."

Seed money came from Bayernkapital, of Munich, Germany; Technologiebeteiligungsgesellschaft tbg, of Bonn; the German Federal Research Ministry; and Apax and Partners, of Munich.

"Wilex is one of the most interesting start-ups in cancer therapy I have seen during the last [few] years," Tom Geimer, of Apax & Partners, told BioWorld International. "The strategy is very convincing and we are glad to be lead investor."

Meanwhile the Wilex team has grown to a staff of 14 and has developed several substances to block the uPA proteolytic enzyme system of cancer cells. "We developed a monoclonal antibody that prevents the binding of uPA to its receptor, we have synthesized antisense-oligonucleotides that block the formation of uPA and its inhibitor inside cancer cells, and we constructed peptides that block the interaction of uPA and its receptor," Wilhelm explained. "Animal studies have shown promising results so far. And knockout mice lacking the complete system can survive and reproduce, so we expect that blocking the system in cancer patients does not have any deleterious effects."

Currently, Wilex is working on lead optimization and conducting preclinical trials. "We anticipate starting clinical trials soon," Wilhelm said. "And we hope to be finished by the end of the year 2000." The company is negotiating with partners for a Phase III study.

Wilex plans to develop both therapeutic and diagnostic products, and is currently looking for cooperation partners to design a detection system for uPA levels. "Of course we have other products in our pipeline, to target cell-specific programs and to develop a gene therapeutic approach," Wilhelm added. "However, much of our progress will depend on access to tumor banks and associated clinics that perform regular follow-up controls. This is a crucial point for an assessment of clinical success." Wilex has established such a network of cooperating clinics and partners, he said. n