Flemish Brabant Leading region for lifetech Inhoud

Innovation fuels economic development 1 Brabant, leading region for lifetech 2 K.U.: source of innovation in the field of medical technology, 7 medicines, food and health Vrije Universiteit Brussel (VUB) and University Hospital (UZB) 9 imec - world-renown centre of expertise for R&D in the field 10 of nanotechnology and nanoelectronics Flemish Brabant, where knowledge is converted into concrete solutions 12 for better health The Leuven region, for years key partner for supplying nanoelectronics 14 in cochlear implants Partnership lifts computer-assisted medicine to a higher level 17 Flemish Brabant: leading enterprise region for medical biotech 20 Healthy, safe food, thanks to leading technology 24 The biggest triple helix players 26 Flemish Brabant, lifetech region par excellence! 27 Flemish Brabant: think Smart, act Hub 28 Contact 32 Colophon 33 Innovation fuels economic development…

Jean-Paul Olbrechts, Delegate for economy, finance and environment province of Flemish Brabant

In Flemish Brabant, we are absolutely convinced of that statement. Plenty To stimulate innovation from this triple helix context is a challenge to of assets all over our province prove our point, starting with the know- which the province continually wants to rise. ledge region around Leuven, the association with healthcare (UZ Leuven), and the world-renown research centre, “imec”. In recent years, this region­ This brochure is your introduction to lifetech in Flemish Brabant. The focus has evolved into a unique myriad of knowledge institutes as well as here is not only laid on the present knowledge institutions, but we will also “knowhow”-driven private companies. The presence of an international present a number of cases that illustrate enterprise initiatives and open airport and the good coverage by the logistics sector in the district of innovation platforms. With these illustrations, we hope not only to inform, Halle perfectly complements the role of the Vrije Universiteit but also to inspire and invite entrepreneurs and people with knowledge- Brussel, together with its associate partners Erasmushogeschool Brussels based jobs to continue to develop innovative lifetech solutions focusing on and AZ (Academic Healthcare Facility), as a Flemish knowledge pool better health. The wide range of lifetech-related knowledge, expertise and in the Brussels region. The added value for the regional development of business activities present in the region are already offering a stimulating our province lies in the synergies and interactions between the aforemen- environment for this. tioned assets. Jean-Paul Olbrechts, The province wants to foster this and, in its role as director and pioneer, Delegate for economy, to give the largest possible boost to innovation. The aim is for the province finance and environment of Flemish Brabant to further excel as a top-end technological knowhow province of Flemish Brabant region, with an emphasis on smart logistics, cleantech and lifetech.

In each of these three areas, Flemish Brabant is home to a unique coming- together of existing knowledge centres, research institutions, innovative companies and supporting measures of authorities and other stakeholders.

1 Flemish Brabant, leading region for lifetech

Flemish Brabant profiles itself worldwide as a leading region with regard to lifetech. Within this multidisciplinary field of science and technology, the region excels in the following areas: pharmaceuticals, medical biotechnology, medical technology, medical devices and functional food. The presence of prominent knowledge institutions and leading researchers, a close network of R&D intensive companies, a very favourable climate for clinical studies and transnational medicine, availability of R&D funding and venture capital and excellent research infrastructure in an upbeat, cultural environment make Flemish Brabant a perfect breeding ground for innovative lifetech solutions. This can be seen from the interesting examples of open Prominent knowledge centres innovation and business cases that are described in this brochure. They illus- trate the special position of Flemish Brabant: a region that is striving, through a and research institutions unique interplay of leading fundamental research, applied research and indus- trial ­applications, for constant renewal and improvements in the field of health, in which the patient’s perspective is central. The development of the lifetech sector in Flemish Brabant is to a very great extent thanks to the presence and development of its well-reputed knowledge centres. Players such as the K.U.Leuven, Vrije Universiteit Brussel, imec and several prominent research departments within the VIB (Flemish Institute for Biotechnology) make the region a fertile soil for lifetech-related research. Some of the best scientists and researchers in the world are hard at work within these knowledge centres. Moreover, the available research facilities in the present knowledge centres attract scientists from all over the world. Therefore a wide range of nationalities is represented in all universi- ties and knowledge centres.

2 Flemish Brabant, leading region for lifetech

3 Leuven University Hospital Campus To bring together education, R&D, translational research and medical care in one location, MEUR 800 will be invested over the next ten years to extend R&D intensive the current hospital campus to the future Health Sciences campus. By 2015, 40,000 visitors a day are expected on the campus, which will employ more than companies 20,000 people. With the extension, Leuven University Hospital (UZ Leuven) wants to strengthen its leading European position.

Approximately 300 companies in Flemish Brabant work within lifetech. A third of those companies have R&D activities within the region. More than 25% of all spin-offs in Flemish Brabant are lifetech-related. Examples are ThromboGenics, TiGenix, reMYND and many others. Large interna- tional life science companies (IDT, Terumo, NXP Semiconductors, etc.) choose Flemish Brabant as their business centre, exactly because of that closeness to leading research, well-educated people with good language Availability of (pre-)seed skills and the pleasant living and working environment in this region. capital, start-up capital and growth financing

Flemish Brabant is characterised by the presence of capital provision throughout the value-adding chain, going from (pre-)seed capital to growth financing. Thus the K.U.Leuven, Vrije Universiteit Brussel and imec have found funding to add value to their knowledge and encourage the establishment of Highly-educated researchers spin-offs. Moreover, there is a dense network of venture capital providers with a focus on lifetech. Examples of these are the Capricorn Health Tech Fund, Gimv (Regional Investment Society ), Vinnof (Flemish Innovation and workers in knowledge- Fund), etc.

based industries The IWT (Agency for Innovation by Science and Technology), set up by the Government of Flanders to support innovation and R&D, invests more than a third of its budget in life sciences research. In addition to financial support, the IWT also contributes to European network activities and training. Flemish Brabant and Flanders in general are renowned for their excellent educational system and high quality of training. The availability of well- In addition to the availability of R&D funding and venture capital, Flanders also educated and highly-trained people with good language skills remains one has many tax incentives to attract R&D activities into the region. An example of the most important competitive advantages of Flanders in comparison of these is the recovery of withholding tax on company income for R&D- with other regions. The close network of research centres and knowledge related activities or the R&D investment deduction. With its allowance for institutions in Flanders with a strong focus on partnership with the indus- patent-related income, Flanders is arguably the most tax-friendly region for try helps attract foreign companies. patent revenues in Europe.

4 Research infrastructure within a rich cultural environment in the heart of Europe

Flemish Brabant invests massively in its science parks, “incubators” and business centres. By doing this, the region wants to offer hypermodern research infrastructure and office space to innovative spin-off companies, as well as to R&D-intensive multinationals and high-tech companies. Favourable climate for clinical • Bio-incubator Leuven is a dynamic environment for young biotechnology companies with intensive R&D programmes. Among others, studies ThromboGenics was set up under this programme. • Another incubator, the Biogenerator, will be accommodated on the “Feed Food Health” campus in . This Feed Food Health project focuses on functional food. Lifetech research in Flanders is encouraged by the favourable framework • Life science companies are also strongly represented in the Haasrode for the execution of clinical studies. Indeed, Flanders has the highest number research park, where large international companies, spin-offs and SMEs of clinical studies per capita in the world. A broad network of expertise have their home base. and supporting services has originated from this large number of clinical studies performed annually in Flanders. In addition, enjoys the fastest Good and affordable accommodation in a green environment, extensive approval procedure for Phase 1 studies within Europe. The excellent test seminar and hotel infrastructure and the renowned wide variety of culinary infrastructure in our hospitals and the very high quality of both execution and cultural choices combine to make Flemish Brabant and Brussels a of the tests and reporting make Flanders the leading region within western particularly attractive place for international enterprises and their employees Europe in the field of clinical studies. to do business.

5 6 KU Leuven: source of innovation in the field of medical technology, medicines, food and health

The K.U.Leuven has a strong focus on research within the life sciences and has vention of thrombosis and other vascular disorders. Further ground-breaking built up extensive expertise in the field of medical technology, medicines, food research in 1993 led to the discovery of tenofovir, which was further developed and health over the years. This focus on life sciences is clearly expressed in the by the pharmaceutical company Gilead Sciences and marketed under the name Health Sciences campus where education, top-level research and patient care Viread. Viread is one of the most used anti-HIV medicines worldwide. are brought together in one location. This campus is home to 1,300 researchers and allows strong cross-fertilisation between research and patient care. Leuven There are different research centres present within the K.U.Leuven that specialise University Hospital, which forms part of this Health Sciences campus, is one of in the development of medicines. To bridge the gap between academic research the most modern and best equipped hospitals in Europe and is accredited by and the pharmaceutical industry, the K.U.Leuven and the European Investment the JCI (Joint Commission International). It has 2,000 beds and 8,500 employees. Fund have set up the Centre for Drug Design and Discovery (CD3). CD3 is a unique technology transfer platform that initiates, coordinates and finances K.U.Leuven Research and Development (LRD) was founded in 1972 as innovative projects for small molecule drug discovery. The new potential medici- one of the first European services for knowledge and technology transfer. nes can form the basis for new spin-off companies or be further developed by LRD ­encourages and stimulates the transfer of knowledge and technology pharmaceutical or biotech companies. Research centres such as CD3 contribute between the K.U.Leuven Association on the one hand, and enterprises and to the international profiling of Flemish Brabant as fertile ground for the phar- societal players on the other. In order to stimulate interdisciplinary research, maceutical and biotech industry. CD3 works together with universities and the a number of research groups work together in horizontal structures, across global pharmaceutical industry and, over the years, has taken the first steps in the faculty and departmental boundaries. development of potential new medicines for, among other things, AIDS, hepatitis C, cancer, arthritis, asthma, epilepsy, Dengue fever and Alzheimer’s disease. Leuven Medical Technology Centre (L-MTC) is an example of this interdis- ciplinary partnership. This centre coordinates 41 research groups within the Another example of interdisciplinary partnership within the K.U.Leuven is the. biomedical and engineering sciences, which leads to a unique combination of LFoRCe conducts ground-breaking research into the relationship between competences and knowhow. L-MTC hosts 700 researchers and professors, food and health. The centre has wide expertise in food technologies, biomedical with specialisations and expertise in areas such as medical imaging, robotics research and social sciences. and automation in health care, bionic systems, controlled administration of drugs, tissue regeneration and biomonitoring.

Leuven has a long and successful tradition in the field of drug development and research. In 1979, researchers at the K.U.Leuven discovered tPA, a protein that dissolves blood clots. Millions of patients have been treated with it, for the pre-

7 As soon as it was founded in 1983, the Centre for Reproductive Medicine (CRG) of the UZ Brussel (Brussels University Hospital) was playing a pioneering role in the development and improvement of reproductive techniques: in-vitro fertilisation, embryo transfer, embryo freezing, new schedules for controlled ovarian stimulation, egg cell donation, etc. The Centre has stood at the international pinnacle of its professional area for decades.

The Diabetes Research Center (DRC) of the VUB develops knowledge, methods and strategies for early diagnosis, prevention and treatment of diabetes. The DRC is the leading partner of the JDRF Center for Beta Cell Therapy in Diabetes, an international consortium headquartered at the VUB campus and supported by the International Juvenile Diabetes Foundation and the European Union. Spin-off Beta-Cell develops new cell therapies and products in the context of diabetes treatment.

The UZ Brussel Radiation Oncology Department is the first centre in the world to use the Vero system. This system enables tumours to be located more accurately and thereby also to be treated more precisely than any other system available to date.

8 Vrije Universiteit Brussel (VUB) and Brussels University Hospital (UZB)

The Department of Medical Oncology of the UZ Brussel and the The department of Industrial Microbiology and Food Biotechnology Laboratory for Molecular and Cellular Therapy, together with the VUB’s researches the use of new functional starter cultures that contribute to dendritic cell bank, have conducted (pre)clinical research since 2002 on food safety and/or providing one or more organoleptic, technological, different formulations of dendritic cells in patients who are suffering from ­nutritional or general health benefits. advanced melanoma. Dendritic cells stimulate the patient’s immune sys- The Toxicology, Dermato-cosmetology and Pharmacognosy team special- tem so that cancer cells are rejected. ises in in vitro experimental toxicology and focuses on the development of functional culturing models for pharmacotoxicological purposes that The Brussels Structural Biology Lab at the VUB has at its disposal an can be used in the earliest stages of development of new chemical com- ultramodern Bio-Nuclear Magnetic Resonance (NMR) centre. NMR tech- pounds to replace laboratory animals. nology makes it possible to determine the dynamic structure of proteins. In addition to applications in fundamental biology, NMR is promising in the The objective of the Center for Neuroscience is to coordinate and op- context of medicine research. This group lies at the basis of the establish- timise all neuroscience research activities at the VUB and the UZ Brussel. ment of spin-off Ablynx, based on technology on camel antibodies. Research interests of the Center for Neuroscience are Parkinson’s disease, epilepsy, neurovirology, multiple sclerosis, cerebral infarction, affective con- The in vivo Cellular and Molecular Imaging Lab conducts pioneering ditions and central regulation of peripheral disorders. research into in vivo imaging of cancer and immune cells. One of the strategic lines of research of the Department of Electronics The Brussels Photonics Team contributes to various societal needs by and Informatics encompasses the generation and processing of physical means of light technology (environmentally-friendly solar energy, energy- images with medical applications (2D/3D imaging and 3D cameras, mm efficient lighting and monitors, ultra-fast optical data communication and waves and THz sensing). ICT and sensors for health and safety). Biophotonics makes it possible to investigate biological and biochemical processes with optical tech- niques and to optimise both the diagnosis and treatment of common illnesses such as cancer and infections. With the help of the Government of Flanders, B-PHOT has in the past invested in world-unique photonic measuring instrumentation and nanoprecision prototype and manufactur- ing technologies.

9 Imec – world-renown centre of expertise for R&D in the field of nanotechnology and nanoelectronics

Development of advanced microsystems

As a growing component of its activities, imec develops solutions for reli- able and cheaper health care. The company is working on technology for Electronics for the health the creation of advanced microsystems for diagnosis and long-term treat- care and medical industry ment, such as neuroprobes, lab-on-chips and chips for DNA sequencing.

imec - set up in 1984 with the support of the Government of Flanders - is a world-renown centre of expertise for R&D in the field of nanotechnology and nanoelectronics. Support of Scientists and engineers work together in the research labs with experts from leading companies, research institutions and universities active in the pharmaceutical research field of electronics, communication, energy and medical sciences. imec has its headquarters in Leuven. Research is being done simultaneously in the Netherlands (Holst Centre in Eindhoven), China, Taiwan and India and the company is represented in Japan imec is also building platforms to support pharmaceutical research. These and the United States. imec employs 2,000 people, including more than 550 platforms enable cells, cell cultures, and tissues to be tested in an intel- industrial resident and guest researchers. ligent and rapid manner. The systems are based on bio-nano interfaces, intermediaries between biological materials and electronics, for which the technologies designed enable communication in both directions via a fine network.

10 Portable and implantable Neuroelectronic Research in body networks Flanders (NERF)

imec and Holst Centre are working together on the technology for port- In the context of NERF, imec also focuses on fundamental research into the able and implantable body networks. Such networks contain microsensors workings of the brain. NERF is an initiative in partnership with the Flemish and actuators. The sensors measure and interpret health parameters; the Institute for Biotechnology and the K.U.Leuven. This research is leading to actuators administer medicines when necessary. Body networks are ex- better knowledge and insights for the pharmaceutical and medical industry tremely reliable, consume little energy, are comfortable to wear and have and is crucial for the research into pathologies such as Alzheimer’s disease a wireless connection for data exchange. and Parkinson’s disease. NERF is housed at the imec campus, where cross- disciplinary research teams make use of the most advanced infrastructure in the world, such as cleanrooms and a new 1,000 m² neurolab.

11 Flemish Brabant, where knowledge is converted into concrete solutions for better health

In the previous sections of this brochure, a short overview has been given Due to its knowledge institutions and the presence of high-tech compa- of a number of major lifetech-related research groups that have built up nies, Flemish Brabant also excels in a number of strongly up-and-coming excellent expertise in the following areas: technologies: nanoelectronics, additive manufacturing (3D software, imaging and printing) and photonics. Innovative applications of these technologies within health care are numerous.

In the following sections, we illustrate innovative collaborative projects in Medicines research and medical a “triple helix” context, within each of the above-mentioned areas. What biotechnology characterises Flemish Brabant is still the partnership between fundamental­ research, applied research and industrial applications, which constantly generates health-related innovations in which the user is central. Medical technology and medical devices

Functional food and related research

12 Fundamental basic research

Applied research

Industrial applications

13 The Leuven region: a long-term key partner in supplying nanoelectronics for cochlear implants

Cochlear is an Australian company listed on the stock exchange and a global leader in the development and production of hearing implants. This company has set up a major R&D establishment in Belgium because of the clinical and technological knowledge in the region.

The company relies almost completely on the Leuven region for develop- ments in the field of nanoelectronics. The K.U.Leuven and imec are impor- tant knowledge partners in this, and the many spin-offs (Easics, ICsense, AnSem) and larger multinationals (NXP Semiconductors) in the vicinity also contribute to research and development.

Open innovation to continuously improve the technology of cochlear implants

Cochlear has approximately 65% of the global market for cochlear implants. Whereas hearing aids just amplify sounds, cochlear implants convert the sound to electrical signals that are transmitted in the cochlea to the auditory nerve. Thanks to this, deaf people and those with extreme A cochlear implant consists of two hearing difficulties can hear sounds again. parts: the implant itself and the speech processor. The implant is In partnership with the K.U.Leuven, imec and companies such as inserted under the scalp in an NXP Semiconductors, Easics, ICsense and AnSem are continuing operation, diagonally above the pinna of the ear. It is a tiny receiver work on refining this technology. Cross-fertilisation between the with a number of electrodes that various partners works to the benefit of all: not only can Cochlear are inserted into the cochlea. The bring better products and new solutions onto the market, it is also speech processor is similar to a hear- possible for the research institutions and companies to strengthen their ing aid and is worn externally. technological expertise.

14 K.U.Leuven: Noise suppression and stimulation terns by which the nerve endings in the cochlea are stimulated. Within this strategies partnership, ground-breaking is work is being done not only to increase The K.U.Leuven (experimental oto-rhino-laryngology and the ­electrical the calculating power of the processor chips, but also to limit their energy engineering department, ESAT) conducts leading-level research into consumption. This is because low energy consumption leads to the use of noise suppression and the design of algorithms. smaller batteries and thus less visible hearing aids and speech processors.

This research has provided considerable quality improvements regarding ICsense and Easics: design of a mixed the efficiency of localisation and comprehensibility of speech in noisy digital-analogue chip environments. This is important because people with a cochlear implant ICsense and Easics have jointly designed a digital-analogue chip for Coch- often have difficulty understanding speech when there is a lot of ambient lear that works together with the processor chip in the speech proces- noise (e.g. in a restaurant, in the classroom or at a party.) sor. Several functions are incorporated in this, such as digitalisation of the noise signals, sound amplification, noise suppression and management of After useful sound signals have been passed on by mathematical calcula- the power that is supplied by the batteries. The chip contains both digital tions and amplified, cochlear implants are able to stimulate the auditory and analogue circuits and they require completely different competences. nerves in the cochlea. This is a challenge. After all, a cochlear implant has Partnership between the two companies has led to a well-functioning only 22 electrodes, while the cochlea itself has 30,000 nerve connections. product. Both applied research and fundamental basic research into neurophysi- ology of the auditory system at the K.U.Leuven have made a significant ICsense: specialising in the design of chips with contribution towards improving cochlear implants. ultra-low power consumption The expertise of ICsense in this story means a significant added value in the efficient management of the available battery capacity so that the speech processor can work at its best. With regard to the internal section, the implant itself, ICsense - in partnership with Cochlear Australia - has also designed the circuits that stimulate the auditory nerves. These circuits must supply the very precise currents that are sent to the auditory nerves at a relatively high voltage. This must be done with ultra-low power con- sumption and with very high reliability and safety.

Easics: unique software solutions for automating chip design In order to further restrict the energy consumption of the speech processor, Easics has designed an ingenious mechanism in which all functionalities are divided up into small partial tasks. These part jobs are only activated when strictly necessary and typically for a very short time, in order to thereby reduce the energy consumption. The company has also developed unique software solutions to automate a number of repetitive and hazardous tasks of chip design. By doing so, it is possible to respond flexibly to market NXP: design of the processor chip to calculate patterns demands and make changes to chip designs efficiently and quickly. of stimulation NXP Semiconductors, the Personal Health headquarters of which is es- tablished in Leuven, has worked with Cochlear for years. In this, NXP is contributing to the development and manufacturing of processor chips for cochlear implants. These processor chips calculate the stimulation pat-

15 imec: chip layout optimisation, prototype and mass production The imec Design Services team, which specialises in digital chip implemen- tation, has investigated the Cochlear chip further from the point of view of power consumption and has assisted Cochlear in optimising the layout of this chip. In addition, the imec ASIC Services team, which specialises in prototype and mass production, has jointly developed the hardware and software for the debugging, characterisation and testing of the prototypes for the Cochlear chip. Both the prototype production and the final manufacture will be performed by imec. Finally, imec also takes responsibility for the qualification of the chip, which includes tests such as ESD (Electrostatic Discharge), latch-up, burn-in, etc.

AnSem: regulating the power management in cochlear implants The wireless power transfer from the speech processor to the implant results in an inaccurate voltage that is not directly usable for the implant. Moreover, the different building blocks need different voltage levels. High voltages are necessary to stimulate the auditory nerves, while digital building blocks are more efficient at lower voltages. AnSem develops the circuits that convert all these inaccurate voltages to all necessary, precisely- controllable voltages and thus regulate the energy management within the cochlear implant. This includes all processes from turning on by itself to the safely switching off the system, in which the safety of the patient is always the prime concern.

In addition to cochlear implants, Cochlear is also aiming at three other product groups: systems that use conduction of acoustic vibrations via the skull, hybrid systems in which a hearing aid and hearing implant are combined in one product and the new Codacs-Direct Acoustic Cochlear Implant (DACI). This last implant has been developed entirely in Belgium. Phase 2 clinical tests are taking place in Belgium and the device will also be manufactured here.

16 Partnership lifts computer-assisted medicine to a higher level

Additive manufacturing (AM) of rapid prototyping technology is a collective Materialise, pioneer in additive manufacturing within term for techniques by which an object is built up layer by layer, starting from Europe a 3D computer model. In recent years, the technique has been applied more From its establishment in 1990, Materialise has grown in a few years to an and more to support computer-assisted implant treatments. international player with more than 800 employees. Materialise not only has the largest production capacity in Europe in the field of additive manufac- Computer-assisted medicine and use of additive manufacturing in the field turing, the company likewise excels in the development of innovative and of medical applications will evolve further in the future. Materialise, Mobelife high-quality software in the field of additive manufacturing. The excellent and LayerWise are working intensively together with academic partners and expertise in both software development and development of AM techno­ are investing expressly in research and development to keep shifting the logy places Materialise among the world leaders in the field of AM. For its boundaries of AM technology. The role of the K.U.Leuven and UZ Brussel exceptional contribution to the AM industry, Wilfried Vancraen, CEO of within the development of AM expertise in the region is unmistakable. Not Materialise, received the prestigious Industry Achievement Award. This prize only do different firms have their roots within this knowledge institution, but is awarded by the Rapid Technologies and Additive Manufacturing Commu- the partnership with various knowledge institutions remains an incentive to nity (RTAM) of the American Society of Manufacturing Engineers. continue innovation and the development of R&D activities. Through the combination of its intensive knowledge in AM technology, it competences in the development of planning software and its expertise in medical imaging, Materialise has a unique position of supplying added value within the domain of digital implantology. Materialise Dental, set up as subsidiary of Materialise, is now a separate entity and an established mar- ket leader in the field of digital dentistry. Materialise is creating important added value in the field of orthopaedic and maxillofacial implants as well.

For standard implants, there are partnerships with multinationals, for which Materialise develops and produces patient-specific surgical guides, as a component of the virtual planning of the operation, which is done in close dialogue with the surgeon. Materialise works closely with spin-offs, such as Mobelife, for the design of complex, patient-specific implants.

17 Mobelife provides a total package for the surgeon per intervention. The bone model and drilling jigs are designed by Mobelife and then manufac- tured by Materialise. The implants themselves, following extensive design and simulation by Mobelife, are manufactured by LayerWise. In addition, Mobelife provides all the necessary preoperative documentation, including an extensive case-specific manual for the surgeon.

Surgical guides or guide plates are drilling jigs, with one or more openings, that enable the surgeon to drill a hole in the bone through these openings to secure an implant. They help the surgeon to place the screws in exactly the predefined direction. This contributes to improving the precision of the surgical treatment. Osteotomies, in which the bone is sawed through in a controlled manner, are also conducted in the same way.

Dr F. Stockmans, K.U.Leuven - Kortrijk Campus, Belgium Dr T. Husby, Ulleval University Hospital, Oslo, Norway

Mobelife, specialist in complex hip revision Mobelife is a niche player in the field of patient-specific implants, in par- ticular for complex hip revision in which these implants are often a last resort for the patient. Patient-specific implants are designed based on the CT images, so the shape is perfectly fitted to the patient’s bone structure and anatomy.

In this context, Mobelife defines the term “patient-specific” in its broadest sense. So when designing the implant, in addition to the bone structure, the bone quality, the load on the bone, the patient-specific muscle-skeleton system, the patient’s weight, as well as other patient-specific parameters are all taken into account in order Prof. Scheerlinck UZ Brussel: “We expect that the number and complexities of hip revision will increase strongly in the coming years. In complex cases, reconstruction with a standard to arrive at an optimal design. Based implant is often complicated. In these cases, an intervention can be planned in advance on the bone quality, even the screw in virtual 3D in partnership with Mobelife. The plastic replicas of the bone and the made- positions are defined before the to-measure pelvic component are very useful for imagining the real situation. Because this operation so that the optimum and component only fits in one way on the bone, there is good control of the implantation posi- most stable fixation of the implant tion, so that the planned screws and the component find optimum support in bone that can be guaranteed. is the least affected. This high-tech innovation will enable us to meet the challenges within hip prosthesis surgery with more confidence and this can only be to our patients’ good.”

18 LayerWise, leading player in AM technology­­ for metal

LayerWise focuses on continuous improvement and innovation regarding the performance of metal components and their cost-efficient manufacture. The applications of metal additive manufacturing in industry are numerous, but there have also been a large number of developments in the medical domain in recent years.

Thanks to collaboration with project partners from the academic world and the medical industry, the company gained a world “first” in 2012 for the production of the first patient-specific implant for the replacement of a whole lower jaw. The complex implant design incorporated several functions and was implanted successfully.

19 Flemish Brabant: leading enterprise region for medical biotech

A tight concentration of knowledge institutions and innovative R&D com- reMYND panies provides for a stimulating environment in which researchers, entre- reMYND was set up in 2002 as a spin-off of the K.U.Leuven. The company preneurs and other stakeholders in the industry can develop their ideas plays an active role in the development of treatments for protein-misfolding and technologies. disorders. This is achieved via its own line of research into new potential Medical biotech guarantees high-quality research and the development medicines and by performing contract research for third parties. of innovative medicines and treatments. Moreover, that development is The company’s own medicine research concentrates entirely on the develop­ achieved according to the most rigorous scientific and ethical standards. ment of disease-modifying treatments in which the aim is to inhibit cellular Quality is central to this and research groups, clinical centres and enter- degeneration or even to stopping it completely. In doing this, the company prises follow the GMP guidelines in their work, imposed by international is responding to an urgent demand from the medical world because the authorities. current treatments are purely symptomatic and thus the underlying degene­ ration is not overcome. This line of research includes disease-modifying A small sample from the wide range of innovative players in this field programmes against Alzheimer’s disease, Parkinson’s disease and diabetes. follows below.

“The nearness of the K.U.Leuven and the University Hospital forms a strong source of knowledge and advice on all possible levels for the company’s own medicine research, the different syndromes, the better understanding of the underlying science, the ability to estimate the severity of possible adverse reactions, advanced statistics, etc. reMYND is always in contact with about a dozen professors. However, these open partnerships are not restricted only to the K.U.Leuven, but extend to a worldwide network of universities and companies. “

Koen De Witte, CEO reMYND

20 ReGenesys TiGenix ReGenesys is the European subsidiary of Athersys Inc., established in TiGenix NV (NYSE Euronext Brussels: TIG) is a leading European cell Cleveland (Ohio, USA). The company is working on the application of therapy company with one commercial product, ChondroCelect®, and a stem cell therapeutic product in clinical practice. MultiStem® cells are a strong pipeline of clinical adult stem cell products for the treatment of derived from human bone marrow and are scaled up to clinical doses via autoimmune disorders and inflammatory diseases. TiGenix was originally a master cell bank. This procedure is approved for use in clinical studies by a spin-off of the K.U.Leuven and Ghent University, which merged with the FDA and in a number of European countries. The MultiStem product the Spanish Cellerix SA in 2011. TiGenix has its headquarters in Leuven is based on the multipotent stem cells discovered at the time by Professor (Belgium) and has establishments in Madrid (Spain) and Sittard-Geleen Catherine Verfaillie’s team; Prof. Verfaillie is the former director of the Stem (the Netherlands). ChondroCelect (a cartilage regeneration product) has Cell Institute in Minneapolis. Athersys Inc. obtained the exclusive rights to been approved by the European Medicines Agency and is sold in Belgium, this technology and concluded a long-lasting partnership agreement with the Netherlands, Germany, the United Kingdom, Finland and Spain. TiGenix Prof. Verfaillie. The appointment of Prof. Verfaillie as the Head of the Stem has a stem cell product, Cx601, for the treatment of perianal fistulas in Cell Institute Leuven (SCIL) led to the establishment of ReGenesys and patients with Crohn’s disease in Phase III; a stem cell product, Cx611, for the creation of a European network for the use of stem cells in cerebral the treatment of rheumatoid arthritis in Phase II; and a stem cell product, infarction and regenerative medicine in general. Meanwhile, it is working Cx621, for autoimmune disorders in Phase I. with UZ Leuven in clinical studies and there are more partnerships with laboratories from the K.U.Leuven. The most important R&D activities of the holding now take place in the ReGenesys laboratories. They are working on a xeno-free product, alternative technologies for scaling up the product and a system for quality control. In addition, other research projects are underway that will provide greater insight into immunomodulation through these stem cells.

21 Formac Pharmaceuticals Formac Pharmaceuticals helps pharmaceutical companies in the development of their medicines by providing innovative drug delivery systems. Formac is a spin-off of the K.U.Leuven. “Although Formac is completely independently managed today, being situated near the university is an important plus point,” says Michiel Van Speybroeck, R&D Director. “The professor who set up Formac 5 years ago still has an advisory role. We also call on the machinery and the expertise of the university for some of the experiments. It’s obvious that Formac’s loca- tion in the Leuven region makes such a partnership with the university easier.”

Okapi Sciences Okapi Sciences develops medicines for the treatment of viral infections for both domestic animals and livestock. The company mainly does research into swine fever and foot and mouth disease. Medicines against viral infections in agriculture and domestic animals are a new market for veterinary science. Okapi Sciences works closely together with contract research companies and academic groups, including the Rega Institute (Faculty of Medicine at the K.U.Leuven).

BETA-CELL BETA-CELL is a private business set up in 1998 as a spin-off of the Diabetes Research Center (DRC) of the Vrije Univer- siteit Brussel. The company develops new cell therapy and One of the Formac labs where in vitro tests are developed that mimic what goes on in the human other diabetes-related products. BETA-CELL is a partner in body after a tablet or a capsule has been taken. the Juvenile Diabetes Research Foundation (JDRF) network, an international R&D consortium that conducts multicentre clinical trials. BETA-CELL therefore has privileged access to the newest technologies within the network and to imple- mentation of its own products in JDRF trials. By being established in the vicinity of the VUB’s research labs, BETA-CELL has direct access to the DRC’s state-of-the-art facilities and the BetaCellBank.

22 ThromboGenics ThromboGenics is a biopharmaceutical company that is dedicated to the of MEUR 375 in pre-payments and milestone payments, plus attractive development and marketing of innovative medicines for the treatment royalties on Alcon’s net takings on ocriplasmin. ThromboGenics and Alcon of eye disorders. The firm’s main product, ocriplasmin, has successfully are planning to the split the costs of developing ocriplasmin for a number completed two Phase III clinical studies for the pharmaceutical treatment of new vitreoretinal indications. of symptomatic vitreomacular adhesive (VMA). The file for ocriplasmin has been accepted for scrutiny in Europe and the file was re-submitted in the In addition, ThromboGenics is developing two new treatments based on USA in April 2012. Ocriplasmin is in Phase II of clinical trials for additional antibodies. These are TB-402 (anti-Factor VIII), a long-acting compound in vitreoretinal conditions. Phase II, and TB-403 (anti-PIGF) in Phase Ib/II for cancer in partnership with Roche. In March 2012, ThromboGenics entered a strategic partnership with Alcon (Novartis) for the marketing of ocriplasmin outside the United ThromboGenics is headquartered in Leuven, Belgium. The company is States. Under this agreement, ThromboGenics can receive up to a total listed on the NYSE Euronext Brussels as THR.

23 Healthy and safe food, thanks to leading technology

Healthy and safe food is a basic need for everyone. Flemish Brabant profiles research-oriented companies that are active in the general area of the food- itself as region with ambitions on healthy food, food production and food related industry. The role of the incubation centre, known as the Biogenerator, processing both for people (Food) and animals (Feed). is to catch spin-offs from knowledge centres and spin-outs from the world of business and to guide them during the first years of their development. Feed Food Health Campus Tienen Within Flemish Brabant, Tienen has a reputation as food town due to The business model of the FFH Campus Tienen is based on the concept of the presence of a number of prominent nutritional companies. With the the Tienen-Leuven axis: the connection between partnerships in the university development­ of the Feed Food Health (FFH) Campus, the region wants town of Leuven and the manufacturing town of Tienen (25 km south-east of to further extend this reputation by creating infrastructure that makes it Leuven). In Leuven, the K.U.Leuven conducts fundamental nutritional research possible to accommodate companies that convert the innovative concepts which at the end of the day may lead to marketable products and new compa- associated with healthy food into manufacturable foodstuffs. nies. The market introduction and the production of these innovative products are done in Tienen at the FFH Campus. The Feed Food Health Campus consists of a science park, an incubation centre and a high-end innovative companies zone. The science park wants to create a In addition to its own particular strengths, Tienen also responds to the wave of lab and services environment for research-oriented companies; the innovative innovation on healthy food that is already discernible in Flemish Brabant. Below companies zone is targeting the production and distribution of the products are some examples of projects that are trend-setters for the future in those that result from the research. The goal is to attract highly technological and industries for which the FFH Campus Tienen was developed.

Sorting technologies for a better, healthy diet

Starter cultures for healthier food The research group Industrial Microbiology and Food Biotechnology (IMDO) of the VUB works together with many academic and industrial partners on a range of projects financed by, among others, the FWO, the IWT, Flanders’ FOOD (incl. Nitrilow and Innocereal) and on a bilateral basis. The research group IMDO has, for example, together with Barry Callebaut, played a pioneering role in unravelling the cacao bean fermentation process. At the same time, the first functional starter cultures have been tested out in the jungle.

24 In partnership with the B-PHOT, BEST is introducing Innovative food production and processing, supported the fluo™ technology by a triple helix environment BEST (Belgian Electronic Sorting Technology) is a specialist in the production Production and processing in the context of health and prevention of sorting machines that are employed in, among others, the food industry. To spearheads the food industry in Flanders. Flanders’Food is the innovation do this, BEST works with a wide range of technologies. From its earliest days, centre of the Flemish food industry that wants to encourage innovation in BEST has worked with knowledge institutions, including the B-PHOT (Brussels Flemish food companies. One of the objectives is to initiate research projects Photonics Team, Vrije Universiteit Brussel) and on several occasions with the in partnership with knowledge institutions, starting from the needs of the support of the IWT. After years of fundamental and applied research from Flemish food industry. the B-PHOT, BEST introduced its fluo™ technology for sorting applications. An example of this is “Sensors for Food”, an initiative in partnership with the research partners imec, K.U.Leuven, Vrije Universiteit Brussel and IBBT. The purpose of this four-year project is to develop sensors that enable the food quality and food safety to be monitored better and more quickly in production environments. The companies taking part in this project can evaluate innovative sensors during the project and optimise them in their own working environment. The IWT has provided a large portion of the funding for this.

Another example of an innovative research project is that of the K.U.Leuven in which they are trying to investigate the cooking time and the food properties of Uncle Ben’s long grain parboiled rice. Professor Jan Delcour and his team in the Laboratory for Food Chemistry and Biochemistry at the K.U.Leuven have obtained a better fundamental insight into what is going on during the different process-technological unit operations that are used Optical sorting technologies for removing aflatoxins in the production of Uncle Ben’s long grain parboiled (partially boiled) rice from food with a cooking time of 10 minutes. In doing this, the emphasis lay on the Another example of technology that BEST, in partnership with the B-PHOT, development of improved food properties. The process has been patented has developed is an optical sorting device (Detox). This technology serves to by MARS NV from Olen. The research was conducted in 2001 on behalf of detect and remove aflatoxins from nuts and dried fruit. The laser technolo- MARS NV, in the form of an R&D business project that was subsidised by gy used is able to detect the extremely low intensity light that is emitted by IWT Flanders. In the preparation of parboiled rice, the chaff, the outermost the fungus. When this type of fungus is layer, is removed from the paddy rice in the country of origin. The resulting illuminated with a particular wave- brown rice is first soaked, then steamed and thereafter dried. In a last step, length, the light is reflected in a the parboiled brown rice is polished to remove the bran fraction and obtain distinctive pattern. Detox can detect white parboiled rice. aflatoxins by this biological charac- teristic, whereas they cannot be dis- Parboiled white rice is pale amber coloured, harder and less sticky than non- cerned with the naked eye. parboiled white rice. It is the property of the rice variety and the conditions of the parboiling and polishing process that determine whether a product will have a short rather than a long cooking time and how sticky it will be.

Since its establishment in 1996, BEST has grown significantly and the company now operates in more than 40 countries.

25 The biggest triple helix players

Knowledge institutions Network of companies Government initiatives

Universities and University Colleges Horizontal network organisations Internationalisation K.U.Leuven Voka - Chamber of Commerce Flanders Investment and Trade www.kuleuven.be Halle-Vilvoorde www.flandersinvestmentandtrade.com www.voka.be/halle-vilvoorde Vrije Universiteit Brussel Innovation www.vub.ac.be Voka - Chamber of Commerce Leuven www.voka.be/leuven Innovation Centre Group T University College www.innovatiecentre.be www.groept.be Leuven.INC www.leuveninc.com IWT KH Leuven www.iwt.be www.khleuven.be CROSSTALKS crosstalks.vub.ac.be Flanders DC www.flandersdc.be Tech Transfer Offices KULeuven and Vrije Universiteit Brussel Cluster organisations Flanders Care Leuven Research and Development DSP Valley (embedded systems) www.flanders-care.be lrd.kuleuven.be www.dspvalley.com Entrepreneurs Technology Transfer Interface Brussels Flanders Bio (biotechnology) vubtechtransfer.be flandersbio.be Enterprise Flanders www.agentschapondernemen.be Flanders Food Strategic research centres www.flandersfood.com imec www.imec.be Industry federations VIB (Flemish Institute for Biotechnology) Unamec (medical devices) www.vib.be www.unamec.be

IBBT (Interdisciplinary Institute for Fevia (food) Broadband Technology) www.fevia.be www.ibbt.be Essenscia (chemistry and life sciences) VITO (Flemish Institution for Technological www.essenscia.be Research) www.vito.be

26 Flemish Brabant Lifetech region par excellence!

Lodewijk De Witte, Governor of the Province of Flemish Brabant

Flemish Brabant excels at the global level in lifetech and life sciences. It is medicines produced in this way are among the best in the world, e.g. a region where a close network of leading researchers and knowledge Viread, one of the most used anti-HIV medicines worldwide. institutions is established in this domain. The pioneering work that is done from here has brought to life numerous international partnership Flemish Brabant also excels in a number of strongly up-and-coming connections, international business activities and spin-offs in the region. technologies, such as nanoelectronics, additive manufacturing (3D The excellent research infrastructure in the region, in conjunction with the software, imaging and printing) and photonics, which are going to change dynamic entrepreneurial climate, attracts scientists and knowledge-based the business landscape of the future drastically. Furthermore, these workers from around the world. Interaction between different countries technologies find numerous applications in the field of lifetech. The cases and worldwide expertise is encouraged via European and regional that are quoted in this brochure illustrate this: the Leuven expertise in support programmes. nanoelectronics and medical expertise with regard to the development of cochlear devices, computer-assisted medicine that uses 3D software, Convergence and multidisciplinarity are key words in this. Working imaging and printing and new inventions in photonics that lead to safer together with medical, biomedical, engineering sciences and other areas is food. encouraged within and between the different university research groups and university hospitals. One of the illustrated examples is Neuroelectronics The assets Flemish Brabant holds within the lifetech domain are Research Flanders (NERF), a partnership between imec, Europe’s largest unmistakable and offer all the necessary potential for the region to be research centre with regard to nanoelectronics, the Flemish Institute for able to continue to develop as one of the most important lifetech regions Biotechnology and the K.U.Leuven. within Europe.

Through the presence of engineering sciences, medical and biomedical sciences at the Flemish Brabant universities and university hospitals, Lodewijk De Witte, Flemish Brabant has a pioneering role with regard to translational research. Governor of the Province of The related research groups have built up excellent expertise in the fields Flemish Brabant of medical imaging, bionic systems, tissue regeneration, biomonitoring, bio-technology, medicine research and others. Belgium is the country in which the most medicines are developed per capita. A large number of

27 Flemish Brabant think smart | act hub

Flanders Smart Hub is

an initiative of the governmental, business and academic world in Flemish Brabant, with the aim of: uniting scientists, leading companies, policymakers, investors and authorities in innovative networks promoting Flemish Brabant internationally and attracting companies and investors developing innovative partnerships and business development Think Smart, activities Act Hub

Flanders Smart Hub acts as a catalyst by: The focus of

arranging brainstorming sessions, seminars, network events, Flanders Smart Hub relies mainly on three industries that excel in scientific and technological knowhow and have an training courses, workshops, etc. together with its partners enormous economic potential: creating and supporting learning networks disseminating information on particular regional or Logistech: transport and logistics, time-critical goods and security European calls for projects Lifetech: health care, medical technology, health promotion and initiating collaborative projects and knowledge transfer functional nutrition between companies, higher education institutions and Cleantech: e-mobility, C2C materials, solar cells and smart grids authorities The development of these clusters is contributing to the further develop- ment of Flanders as an innovative region.

28 Flemish Brabant

Zaventem Leuven Brussels

+ 8.500 researchers International airport  Favourable business climate for companies + 110 spin-offs with an extensive  High added value per inhabitant cargo area  International collaboration + 101.000 students

29 30 Flanders Smart Hub today

The Flanders Smart Hub Community has 5,300 contacts

Operates around the following topics: sustainable logistics, e-mobility, medical technologies, sustainable building, smart grids, smart logistics, innovation in health care, etc.

Partners

Voka - Chamber of Commerce Flemish Brabant, K.U.Leuven Research and Development, ERSV Flemish Brabant, Haviland, imec, Interleuven, Leuven. INC, POM (Provincial Development Company) Flemish Brabant, Province of Flemish Brabant, City of Leuven, the Company, Flemish Institute for Logistics, Vrije Universiteit Brussel. Become a part of With the financial our community now! support of Sign up Our activities are supported financially by the European Regional Development Fund, Hermes Fund of the Government of Flanders, the Province of Flemish Brabant, POM (Provincial Development for our newsletter. Company) Flemish Brabant and Voka - Chambers of Commerce Flemish Brabant.

31 Contact information

Do you want to innovate, but are unaware of how to start? Do you have an idea, but no clue on its feasibility? Do you want to cooperate with a knowledge institute or knowledge centre? Did you do research, but your company is still searching for a plan to actually produce? Do you want more info on Flanders Smart Hub or one of our partners? Give us a call!

Offices:

Voka - Chamber of Commerce KU Leuven Research & Development Halle-Vilvoorde vzw Waaistraat 6 Medialaan 26 B - 3000 Leuven B - 1800 Vilvoorde T: +32 16 32 06 45 T: +32 2 300 58 02 F: +32 16 32 65 15 F: +32 2 255 20 30

[email protected] www.flanderssmarthub.be

32 Colophon

Flanders Smart Hub Medialaan 26 1800 Vilvoorde T: 02 300 58 03

[email protected] www.flanderssmarthub.be

Text Katja Van Remoortere - Flanders Smart Hub

Co-ordination & Editing Sara Geris - Flanders Smart Hub Katja Van Remoortere - Flanders Smart Hub

Concept and Design www.blau.be

Printer Drukkerij Lamine

Photography Province of Flemish Brabant, K.U.Leuven, Vrije Universiteit Brussel, imec, Pieter-Jan Peeters

Sincere thanks to Governor Lodewijk De Witte, Delegate Jean-Paul Olbrechts, NXP, ICsense, Easics, AnSem, Materialise, Cochlear, Experimental ORL K.U.Leuven, ESAT K.U.Leuven, Mobelife, LayerWise, reMYND, ReGenesys, TiGenix, Formac Pharmaceuticals, ThromboGenics, Okapi Sciences, BETA-CELL, Feed Food Health Tienen, BEST, B-PHOT and to all theFlanders Smart Hub partners.

Editor: Voka CCI Halle-Vilvoorde, P. Hegge, Medialaan 26, 1800 Vilvoorde. Vilvoorde, June 2012.

All rights reserved. Nothing in this publication may be reproduced and/or published by means of printing, copying or any other method whatsoever, without the prior written approval of the publisher. Europese Unie Europees Fonds voor Regionale Ontwikkeling