September 15, 2007 (Vol. 27, No. 16)

Funding Has Ramped Up 67% in 10 Years and Academic Innovation Is Fueling Start-Ups

Flanders, the northern part of Belgium, is trying to give the country’s claim to fame, chocolate and beer, a run for its money. The area has been sporting a growing biotech industry, and the Flemish government is making strides to bring it to the forefront.

The age-old chocolate and brewery businesses annually rake in upward of E2,792 million and E626 million, respectively. The comparatively new biotech industry made about E429 million in 2005.

Touting the area as a biotech cluster, venture capitalists and the government have ramped up funding. Research institutes and universities in the area fuel innovation, often giving rise to spin-off companies. Established firms provide infrastructure as well as discovery and development expertise.

Flanders would not a cluster be if it was not for the fact that it is only about 5,220 square miles. This means that most of the 39 companies located within the region as of 2006 are within an hour’s drive from each other. Flanders could be a successful long-term hub because of its proximity to the U.K., Germany, France, The Netherlands, and Luxembourg.

More than 20 of the firms based in the region are dedicated biotech companies. In fact, Belgium ranks third in terms of the number of drugs under development related to country size, with 8.6 candidates per million capita in clinical trials. The U.K. has 14.3, and the U.S. has 11.4.

The Flemish region employs 20,000 people in the life sciences, there are 6,100 researchers in life sciences at universities and research institutes, and a yearly outflow of 3,600 graduates in this field.

A Virtual Institute

The Flanders Institute of Biotechnology, or VIB, is a so-called virtual institute because its research departments are based at four universities: Ghent University, the K.U.Leuven, the University of Antwerp, and the Vrije Universiteit Brussel. Hasselt University is also located in Flanders, and all five have their own technology transfer arm.

VIB was born in 1996 with activities in basic research, technology transfer, and science communication. The Flemish government’s investment in VIB is made on a five-year basis. The latest totaling E198.295 million is almost twice the initial fee. The total budget currently is E70 million, three-quarters of which goes to the life sciences and the rest to agricultural research.

The ultimate goal for VIB is to stimulate economic growth in this region. The organization leverages its portfolio of 150 patent families through R&D and license agreements. It even operates a bio-incubator for biotech start-ups. In fact, research at VIB has resulted in five spin-offs located in Flanders.

VIB Spin-offs

Devgen( uses RNAi tools to discover pest control and human drug targets and find ways to improve compound screening. Within human therapeutics, Devgen focuses on diabetes, obesity, and arrhythmia, with three different programs are currently in lead optimization.

Devgen’s goal is to partner some drug candidates, and use revenues earned for internal R&D. Devgen Healthcare has collaborations with Johnson & Johnson (JnJ), Metabolex, Genentech, and Sumitomo Chemical. Currently, the company’s driver certainly is its crop-protection division, reaping over 94% of 2006 revenues.

Ablynx’ ( expertise is in Nanobodies®, a class of antibody-derived therapeutic proteins that combine the advantages of small molecule drugs and conventional antibodies.

Researchers at Ablynx discovered that members of the family Camelidae possess fully functional antibodies that lack light chains. The resulting heavy-chain antibodies contain a single variable domain (VHH) and two constant domains (CH2 and CH3). These newly discovered VHH domains form the basis of Nanobodies, explains Eva-Lotta Allan, CBO.

Nanobodies outperform conventional therapeutic antibodies, Allan points out. While small molecule drugs can take between 30 and 60 months, and conventional antibodies as much as 46 months from lead discovery to preclinicial development, Nanobodies typically take only 25 to 27 months, says Allan.

ALX-0081, currently in Phase I, targets von Willebrand Factor (vWF) to reduce the risk of thrombosis in patients with acute coronary syndrome. While Plavix and aspirin act at the platelet-activation stage, and ReoPro even later at the platelet-aggregation stage, ALX-0081 acts before these at the platelet-adhesion stage, explains Allan.

ActoGeniX ( touts its unique technology for the oral delivery of biopharmaceuticals. VIB and Ghent University researchers invented the TopAct™ (Topical Active release) technology, based on living nonpathogenic microorganisms.

ActoGeniX engineers Lactococcus to express and secrete human therapeutic proteins and peptides. The company’s initial focus is on inflammatory bowel diseases. ActoGeniX is preparing to initiate Phase II studies of TopAct™IL-10 (AG011) in Crohn’s disease and ulcerative colitis in the first half of 2008.

Pronota ( also benefited from discoveries at VIB and the University of Ghent. Its eye is on diagnostic development. In the last 15 years, only nine proteins have been approved by the FDA as diagnostic tests, according to Koen Kas, Ph.D., CSO. He hopes Pronota’s technological capacity to separate low-abundance proteins from high-abundance proteins and verify and validate markers will give rise to a number of diagnostics.

Pronota’s MASStermind™ is different because of its high information content, according to Dr. Kas. MASStermind delivers both a profile and the identity of each of the underlying protein biomarkers.

The company is focusing on oncology for the development of biomarker-based diagnostic products. The response rate to existing medicines in oncology is the lowest compared to any other therapeutic area, Dr. Kas points out. Thus, Pronota is developing tests not only to identify the disease at an earlier stage, when a patient has more of a chance to respond to therapy, but also to predict the outcome of a particular treatment.

Start-ups With a Pipeline

While all the VIB off-shoots are relatively young with either an early-stage or a preclinical pipeline, another spin-off has a rather full pipeline at all stages of development. Movetis ( was formed on the basis of a portfolio licensed from JnJ companies just this year. In fact, Movetis has no lab space of its own.

The acquired drugs are all related to gastrointestinal (GI) disorders. “JnJ considers these drugs lifestyle drugs and hence we decided to divest the portfolio,” explains Frederick Wittock, communications director, JnJ. Movetis has one drug in Phase III evaluation, one in Phase II studies, and two that are entering or recently completed Phase I studies. The company also gained four preclinical compounds and two discovery platforms. Movetis’ goal is to generate revenues by 2010.

Lead product, Resolor, is an enterokinetic compound that restores the natural movement of the bowels. According to the company, Resolor has been proven in three Phase III studies to be effective and well tolerated. The drug has a favorable benefit/risk profile compared to laxatives or other 5 HT4 agonists, says Dirk Reyn, CEO. Movetis expects to file an NDA by beginning of 2009.

TiGenix ( is another example of a start-up with a late-stage candidate. It is built on technologies developed at the Katholieke Universiteit Leuven and the Universiteit Ghent related to regenerative medicine.

The company focuses on the development of treatments for damaged and osteoarthritic joints. Regenerative cell therapy bridges the gap between symptomatic relief of current therapies used earlier in life like pain killers and microfracture, and replacement therapies used later, like joint revision and joint replacement, states Gil Beyen, CEO. The company filed an MAA in the first half of 2007 and plans to file a BLA during 2008 for ChrondoCelect, its lead product.

ChondroCelect, used in combination with autologous chondrocyte implantation (ACI), has a more potent cell population than standard ACI procedures, Beyen states. TiGenix tests cell populations taken from a patient on an in vivo assay with gene-expression profiles for 150 positive markers and 60 negative markers.

In the future, TiGenix also aims to couple ChrondoCelect with a hyaluron-based scaffold, Hyalograft-C, for easier and faster surgical procedures. Italian company Fidia Advanced Biopolymers has developed this biomaterial. The company is also developing MeniscoCelect for the regeneration of meniscus.

Just two years older than TiGenix, ThromboGenics ( is another new company with compounds in its pipeline. It focuses on therapeutics for conditions related to the vascular system. The company’s business model is to develop a compound until the proof-of-concept stage and then partner it.

ThromboGenics’ lead product, microplasmin, is in Phase II trials for eye and thrombotic diseases. TB-402 is in Phase I evaluation as treatment for DVT and atrial fibrillation.

Microplasmin is a truncated form of plasmin, an enzyme that dissolves protein formations that are crucial to the formation of a thrombus. Given prior to surgical vitrectomy, the drug will induce posterior vitreous detachment leading to safer and more rapid surgery with fewer complications, points out Jean Marie Stassen, Ph.D., senior director R&D.

Microplasmin, a direct acting thrombolytic, is also in Phase II trials for acute ischemic stroke, deep vein thrombosis, and acute peripheral arterial occlusive disease. Once microplasmin leaves the site of the clot and travels into the systemic blood circulation, it is inactivated by a blood protein alpha-2 antiplasmin, which means that the risk of bleeding away from the treatment area is minimized.

Financial Incentives

To keep these companies in Flanders, the Flemish government is striving to reduce corporate tax by fiscal deduction of R&D costs at a rate of 15%, with a tax credit for companies that do not pay taxes yet. To further bring down research expenses to the levels found in neighboring countries, a one-time tax exemption for R&D personnel has been introduced.

To assert its support of the industry, over the last 10 years the Flemish government’s annual funding increased 67% to E38.1 million.

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