Eastern promise

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Claire Skentelbery investigates the reasons behind the popularity of UK university town Cambridge as an incubator for science start ups.

A recent Newsweek article identified Cambridge and its regions as one of the most likely areas in Europe to challenge Silicon Valley for high-technology driven innovation.

The Cambridge cluster of companies is unique in Europe and ranks among the top five biotech centres in the world. It was one of the earliest clusters in Europe, growing rapidly with massive injections of investor funding to reach a critical mass that stamps it as a mature industry. The cluster has its roots in one of the strongest academic soils in the world. Scientific and technical excellence has thrived in Cambridge for 1000 years and biotechnology emerged into an environment that already boasted a high-tech IT industry. But the factor that has ensured a healthy long term prognosis is perhaps the region’s pure commercial strength. A biotechnology industry formed spontaneously in response to market demand and the cluster retains a commercial edge unseen anywhere else in Europe.

Biotech cluster
An industrial biotechnology cluster emerged in Cambridge in the early 1980s, created by existing electronic and computing industries. Initial companies were founded on the Cambridge Science Park (owned by Trinity College, University of Cambridge), which was built to attract computing businesses. The number of biotechs grew steadily until the mid-1990s when a global explosion of investment in high-tech industries accelerated company creation to a rate sustained until the global stock market decline in 2001-02.

The success of the Cambridge Science Park spawned the development of additional science and business parks typically within a 15 mile radius of the city. Outside of Cambridge the most notable locations for biotech companies are Granta Park at Great Abington and Chesterford Research Park close to Saffron Walden. Other Cambridgeshire business parks offering spaces to biotechs are located at Histon, Melbourne, Royston, Cambourne and Cambridge Research Park near Waterbeach. There are other nearby towns which seem to attract small groups of biotech companies such as Huntingdon, Ely and Stevenage.

In contrast to the vast majority of other European centres, the Cambridge cluster of companies grew before biotech incubators were even thought of. The first and largest incubator opened only in 1998 at Babraham, and is run by Babraham Bioscience Technologies and funded by the Biotechnology and Biological Sciences Research Council.

This institute is part of the world-leading academic research foundation which supports the cluster, and boasts 15 Nobel prize winners in medicine and chemistry since Fred Sanger was awarded the Nobel prize for chemistry in 1958 for his work on the structure of proteins. Francis Crick and James Watson remain perhaps the most famous winners, with their recently commemorated discovery of the structure of DNA.

Already possessing a world-leading biotech research profile through organisations such as the University of Cambridge, Institute of Biotechnology and Babraham Institute, the cluster received a significant boost through the location of the major European effort for the Human Genome Project at the Sanger Centre, located within the Wellcome Trust Genome Campus alongside the EMBL-EBI (European Molecular Biology Laboratory-European Bioinformatics Institute).

Critical mass
The cluster continues to develop today, driven by a need for more laboratory space. Its growth is also helped by the University of Cambridge adopting a more proactive approach to commercial application of its academic research.

As the cluster has evolved over the past two decades, the critical mass of industrial biotechnology has attracted an equal weight of technical and business service providers, creating an area rich in academic and commercial science, well served by local support providers.

With over 180 biotechnology companies and even more service providers, Cambridge has achieved a mass that yields some shelter from global storms and has created a fully served community attracting investors from across the globe.

The Cambridge cluster has a dynamic history when it comes to company business strategy. When industrial biotechnology emerged in the 1980s, the race to bring therapies to market was paramount. As the world awoke to the possibilities of biotechnology, and investment soared, researchers responded accordingly: a significant number of platform technologies were cultivated, with the promise of introducing groundbreaking methods of developing new and improved therapies.

Now, as investors are more cautious, the trend is swinging back towards the apparently safer product pipeline. Pharmaceutical companies are looking to ’in-license’ development compounds after Phase I or Phase II clinical trials. And, because such late-stage compounds are seen as the root of the value of smaller companies, the investors are also keen to see this kind of development.

Building on biology
The development path for new knowledge in the life sciences means that its commercial exploitation can no longer be contained within the biological sciences, if indeed it ever could. One of the strengths of the wider Cambridge cluster is its prowess in chemistry, encompassing combinatorial chemistry, combinatorial biochemistry, and medicinal chemistry. A historical strength in chemistry has attracted key scientists to the region but, as across Europe, the availability of chemists is a limiting factor and an experienced medicinal chemist is worth his or her weight in gold.

However, the need for cross fertilisation does not stop there. Much of the new wave of drug development in the post-genomic and proteomic era is powered by information on biological systems. Biology and biotechnology are moving from a base in the reductionist science of molecular biology to a much more integrative approach to biology.

Metabolic pathway analysis, whole cell and organ biology, and even the modelling of toxicological effects of drugs require the assimilation of detailed biology through computing. The European Bioinformatics Institute at Hinxton is one of Europe’s hubs in bioinformatics and serves as a magnet for computational biologists of all kinds.

The non-biological technologies that Cambridge has in abundance - automation, electronics, precision engineering, miniaturisation, and telecommunication - are essential for products such as biosensors and biochips, where biology is just a provider of specialist components. A recent survey of bioscience companies identified necessary key skills in these technology areas, and many of these can be provided by other companies in the region.

People power
There are dozens, if not hundreds of centres in Europe with all the right ingredients to develop successful biotechnology clusters; an excellent academic foundation, progressive research and incentives to commercialise breakthroughs - so why is Cambridge so far ahead?

The answer is people: the Cambridge cluster is characterised by an entrepreneurial culture found in few places outside Silicon Valley. Many of the same company founders that started the first biotechnology companies in Cambridge are still active, often on their fifth or sixth company start up. The consolidation of the pharmaceutical industry around Cambridge released highly skilled managers into the cluster, further boosting start-up achievements, and a glance at the board of directors for any biotech company reveals a wealth of success.

The overwhelming mind-set in Cambridge is that anyone can start a biotech company. In fact the rate at which new start-ups are emerging has not significantly slowed even in the face of reduced investment.

The whole cluster functions as a well networked community. This is vital if patented technologies, the life blood of a company, are to find applications across disease areas and countries. Through the Eastern Region Biotechnology Initiative (ERBI), a regional membership-based biotech network started in 1997, business and scientific company members meet regularly to discuss current topics, reaping the benefits of close relationships with leading biotechs of all sizes.

Regular network meetings are supported by an Annual Biopartnering Exchange Conference, next scheduled for 5-7 May 2004, which is attended by over 400 life science executives and is now in its sixth year. ERBI also helps support company operation through its purchasing schemes, biotech-specific training programmes, job finding service and other activities driven by specialist networks including Human Resources, Finance and Business Development.

Such a network, not possible without the enthusiasm and commitment of the member companies has helped ensure the high profile of biotechnology in Cambridge and attract funding from investors in an increasingly cautious global market.

Acknowledgements

Claire Skentelbery

The cluster in 2003

180 biotech companies
250 specialist service providers with biotech expertise
30 research institutes and universities
20 multinationals in pharmaceuticals, agrochemicals and biotechnology and food
Four leading hospitals involved in research and working with biotech

Venture capital
The Cambridge cluster holds a high profile in the Venture Capital (VC) world. In the current quiet market, Cambridge companies have received some of Europe’s highest VC investments in the past two years

Venture Capital company	Biotech
Abingworth	Akubio, Astex, Solexa, Lorantis
Avlar BioVentures	Amedis, Amura, De Novo Pharmaceuticals, Paradigm Therapeutics
Merlin Ventures	Amedis Pharmaceuticals, De Novo Pharmaceuticals, Arakis, BioWisdom
Quester	Lorantis, Cyclacel, De Novo Pharmaceuticals
Cambridge Gateway	Cambridge Biotechnology, De Novo Pharmaceuticals
Apax	Celltech, Ionix Pharmaceuticals, RiboTargets (now Vernalis), Xenova
3i	Arakis, Amura, Adprotech, KuDOS Pharmaceuticals

Technology transfer

The University of Cambridge has strong links with many local biotech companies. The university’s commercialisation arm, Cambridge Enterprise, transfers technology arising from the university’s research, including medical science at Addenbrooke’s Hospital, to companies - both new and established.

David Secher, director of the research services division in the university points out: ’Cambridge has a long tradition of working with industry and spinning out companies. Building on this success, the university has invested in a strong team which contains the commercial and legal expertise to turn the results of world-class research into practical and economic benefits’.

Specialist staff work with academics to review over 140 inventions each year and plan the best route for commercialisation and intellectual property protection. Cambridge Enterprise seeks commercial partners from start-up biotechs to multinational pharmaceuticals to develop new products.

A recent example of commercial partnership was the June 2003 worldwide exclusive agreement with Paradigm Therapeutics, a Cambridge-based biotech firm, to develop new medicines to combat chronic pain, a multi-billion pound market, with a high, medical need.

Recent examples of companies originating from the university are:

Akubio (formed 2001): Sensitive acoustic detection technology for rapid, label-free screening of drugs and diagnosis of viral and bacterial infections (Chem. Br., May 2003, p42).
Astex Technology (formed 1999): A structure-based drug discovery company using high throughput X-ray crystallography technology for the rapid identification of novel drug candidates.
Solexa (formed 1998): DNA sequencing technologies and development of methods for chemical analysis at molecular level.
KuDOS (formed 1997): Discovers and develops innovative products that modulate human DNA repair to treat human disease, particularly cancer.

Company Profiles

Acambis is a world leader in the development of vaccines to prevent and treat infectious disease. It is a fully integrated biotechnology company, incorporating research, development, clinical, regulatory, manufacturing, sales, and marketing functions. Acambis is headquartered in Cambridge, UK and has facilities in Cambridge, Massachusetts.
Acambis has one of the broadest development pipelines of any vaccines company, with nine products undergoing clinical trials, including vaccines against smallpox, West Nile virus, yellow fever, Japanese encephalitis, dengue fever, traveller’s diarrhoea and typhoid.
KuDOS Pharmaceuticals is focused on the discovery and development of specific inhibitors of DNA repair for use in treatment of cancer and a range of other diseases.
KuDOS was incorporated in 1997 by Stephen Jackson, Cancer Research Campaign Technology and the University of Cambridge. In May 1999 the company announced an initial funding of ?5 million by a group of UK-based venture capital organisations comprising Advent, Schroder Ventures and 3i.
Xention Discovery is a drug discovery company that focuses on ion channels. The company’s proprietary AutoPatch technology is a functional screening system that directly measures currents across cell membranes allowing the rapid screening of small molecule drugs against ion channel targets in a functional and automated fashion.
Xention uses its screening platform to accelerate the discovery of novel small molecule drugs that modify ion channel function. It is currently screening a number of targets in the cardiovascular and neurology areas and is developing small molecule expertise focused around these targets to identify lead drug candidates.
Domantis develops a range of platform technologies for the in vitro evolution and engineering of recombinant proteins. The field of recombinant proteins is showing immense potential and is expected to yield both new medicines together with vital diagnostic and proteomic tools. Domantis is pursuing commercialisation strategies in all of these target areas.
In addition to their own research, Domantis also supports the development of a range of new technologies in this field based on the work of founders and their colleagues at the MRC’s Laboratory of Molecular Biology.
Cytomyx is a Discovery Research Organisation (DRO) specialising in the provision of services that support the early stages of the drug-discovery process.
Cytomyx is able to provide the international pharma-biotech industry with a complete ’target-to-screen’ discovery research platform, supporting them in the identification and validation of novel drug targets. It is also using its technology platform to generate a database of novel, validated targets in various disease areas that can be partnered for further development.
Ionix Pharmaceuticals is Europe’s first biotechnology company dedicated to the discovery of novel analgesic drugs. Ionix focuses on pain associated with chronic debilitating diseases such as osteoarthritis, rheumatoid arthritis, multiple sclerosis and diabetic neuropathy.
Ionix uses proprietary ion channel drug targets that are involved in the perception and signaling of pain, with a focus on the discovery of drugs that act in the peripheral nervous system. This will allow the discovery of highly selective and efficacious medicines, without the side effects that are associated with today’s drugs that act in the central nervous system. Current product development programmes address unmet medical needs in the fields of acute post-operative pain, cancer pain, chronic inflammatory pain and chronic neuropathic pain.
Cambridge Antibody Technology (CAT) is a UK-based biotechnology company using its proprietary technologies and capabilities in human monoclonal antibodies for drug discovery and drug development. CAT is a leader in the discovery and development of human therapeutic antibodies and has an advanced proprietary platform technology for rapidly isolating human monoclonal antibodies using phage display systems. CAT has extensive phage antibody libraries, currently incorporating more than 100 000m distinct antibodies. These libraries form the basis for the company’s strategy to develop a portfolio of antibody-based drugs. Humira, the leading CAT-derived antibody, which was isolated and optimised in collaboration with Abbott, has been approved by the US Food and Drug Administration for marketing in the US as a treatment for rheumatoid arthritis. Six further CAT-derived human therapeutic antibodies are at various stages of clinical trials.
Amedis Pharmaceuticals is a chemistry-driven drug discovery company and a pioneer in the use of silicon medicinal chemistry for the development of innovative pharmaceuticals. Amedis is exploiting its unrivalled expertise in silicon chemistry to generate a robust development pipeline of silicon containing compounds. These silicon switch compounds leverage the unique properties of silicon to overcome deficits in the properties of existing drugs or failed development compounds.
Benefits include enhancements of the pharmacokinetic and/or pharmacodynamic profiles, and improvements to the efficacy and selectivity of the silicon switch compound. Amedis is also applying its silicon chemistry expertise to the development of novel drug candidates for a sustainable long-term R & D pipeline.
Alizyme’s drug R & D programmes are targeted at developing prescription therapeutic drugs offering patient benefit, competitive advantage and substantial market opportunity. Alizyme is focused on the treatment of obesity and related diseases such as Type II diabetes and gastrointestinal disorders including irritable bowel syndrome, inflammatory bowel disease and mucositis, a side effect of cancer therapy.
Alizyme’s product development portfolio consists of four product candidates and a colonic drug delivery system, COLAL. All four product candidates are in clinical trials. Alizyme owns or has exclusive rights to its intellectual property portfolio.