Washington Editor

Editors' Note: This is part two of a three-part series on biotechnology development in Flanders, Belgium. Part one ran in Wednesday's issue, and part three will run in Friday's issue.

GHENT, Belgium - University-driven research serves as a fountain of new discoveries and technologies for biotechnology, and it's no different in the Flanders region of Belgium, where several of the schools date back centuries.

As a result, Flemish biotech companies have a strong tie to local research, although that research also draws foreign interest. In the area, there are a dozen public research organizations - five universities and seven research institutes, as well as the Flanders Interuniversity Institute for Biotechnology (VIB).

The Catholic University of Leuven was founded in 1425 and is the oldest in the country. These days, in addition to its 28,000 undergraduate students and active technology transfer office, it also houses offices and research facilities for four biotech companies with clinical-stage pipelines.

U.S.-based TorreyPines Therapeutics Inc. recently opened an office in Leuven to pursue some of the research opportunities that spin out of the school. The company has raised $68 million to date through three financing rounds, with some of that funding coming from a Flemish investor, GIMV.

"It's very dynamic here," explained Angelico Carta, the managing director of TorreyPines Therapeutics Europe NV, "with a lot of attention for biotech companies."

TorreyPines, which is focused on central nervous system disorders such as migraine and Alzheimer's disease, already is operating clinical research sites in Belgium.

Other companies with operations in Leuven include Tigenix NV, a five-year-old firm spun out of that university, as well as the University of Ghent, to focus on regenerative medicine for joint surface repair in osteoarthritis. The company is expecting results early next year from a randomized Phase III trial of its ChondroCelect in 118 patients being treated through autologous chondrocyte implantation, a surgical procedure for cartilage defects.

Diatos NV, a subsidiary of a French firm of the same name, has established a research division in Leuven to explore its tumor-selective prodrug program. The company is not in the business of drug discovery, but rather uses peptide technologies to target delivery to tumor cells, and to that end is about to enter clinical studies with prodrugs of doxorubicin and paclitaxel.

Also doing business in Leuven is Thromb-X NV, the research and development division of ThromboGenics Ltd., of Dublin, Ireland. It is developing recombinant microplasmin, a truncated form of plasmin, for patients with vitreoretinal disorders. ThromboGenics also has promoted its early development of placental growth factor as an angiogenic candidate for conditions such as ischemic heart disease.

The companies bring VC investment and an economic base, but it's the research that is perhaps the pride of Belgium.

Among notable scientists here are Walter Fiers, who decoded the chemical structure and functional meaning of a full gene and a complete genome. Also, there's Erik De Clercq - he discovered and developed multiple anti-HIV therapeutics and worked to open the field of nucleotide analogues as broad-spectrum antiviral medications. As executive director of the Joint United Nations Program on HIV/AIDS, Peter Piot was the first to warn of HIV's heterosexual transmission characteristics.

Commercial successes also have arisen from research here. ThromboGenics founder Désiré Collen's efforts led to the potential of tPA (tissue plasminogen activator), a cardiovascular drug marketed worldwide by Genentech Inc., of South San Francisco. Jeff Schell and Marc Van Montagu developed the Agrobacterium tumefaciens DNA transfer technology, which now is used around the world to introduce foreign genes into plants - it paved the way for the establishment of Plant Genetic Systems NV at the University of Ghent, one of the first agricultural biotech companies now operating as Bayer BioScience NV. Perhaps most recognizable by name is Janssen Pharmaceutica NV, a company founded by the late Paul Janssen, who, with his teams, developed more than 80 drugs.

For about 40 years, Janssen has been a part of Johnson & Johnson, a major investor in the region that also bases its J&J Pharmaceutical Research & Development division in Belgium. In the last five years, J&J has dropped $100 million into its Flanders operations, largely due to the existing research base and academic tradition.

J&J, of New Brunswick, N.J., also owns Tibotec Pharmaceuticals Ltd. and Virco BVBA, two Mechelen, Belgium-based companies with complementary HIV therapeutic and diagnostic programs, respectively.

Genzyme Set To Open Flemish Production Site

Among widely recognized names operating in Flanders is Genzyme Corp., which is putting the finishing touches on a large manufacturing facility in Geel set to open in September.

"At Genzyme, we're building a sustainable future," said Erik Tambuyzer, Genzyme Europe's senior vice president of corporate affairs, "and a strong presence in Europe is a large part of that."

Of the 7,000 employees of the company, which is headquartered in Cambridge, Mass., about 2,000 are in Europe. Genzyme Flanders NV opened its doors nearly four years ago after taking over the assets of a joint venture it held with Pharming NV, a Dutch firm that was seeking to dissolve its Belgian operations. Since then, the Flemish site has been used for biopharmaceutical production, and for the most part that will remain the case, though the facility also is being used to develop cell culture technology.

Genzyme Flanders has invested more than €150 million in its facility, which is located amidst a lush rural stretch between Brussels and Antwerp. Of its almost 140 employees, about 100 are holdovers from the prior Pharming business. Genzyme Flanders kept all those employees, considering their competencies vital to the manufacturing site's expansion. It will be used to produce a single product for the parent company's vast portfolio, though specifics were not discussed by Tambuyzer, whose background is representative of a common thread among many in the Flemish biotech community: He is a co-founder of Innogenetics NV and did his doctoral studies at the University of Leuven.

He did note that Genzyme, which regards itself as a small company with a global presence, has sought to expand its reach in part to hedge its financial risks by operating single-product manufacturing facilities in different parts of Europe and the U.S. The Flanders site certainly fits into such plans.