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Jun 1, 2008 (Vol. 28, No. 11)

Norway's Oncology Efforts Are Coalescing

The Oslo Cancer Cluster Is at the Heart of a Burgeoning Movement

  • Most biotech companies in Norway are focused upon oncology, and 80% of the nation’s cancer research is located in or around the capital. Therefore, the formation of the Oslo Cancer Cluster (OCC), a partnership between industry, research institutions, government, and the Norwegian Cancer Society is a logical development.

    The vision of OCC is “to transform world-class cancer research into new cancer diagnostics and treatment and thereby improve the lives of cancer patients,” explains Jónas Einarsson, chairman of the board of the Oslo Cancer Center. Established about one year ago, OCC now has 40 members including big pharma, research organizations, and many biotech spinouts. “We aspire to be regarded as the most innovative cluster for cancer diagnostics and treatment in Europe,” adds Einarsson.

    Central to OCC is Radium Hospital, which was founded in 1932 and has a world reputation for cancer treatment and research. In fact, Norwegian biotech with a cancer focus got its start at Radium Hospital Research Foundation, which was founded in 1986 to commercialize cancer research.

    In 2006, the Norwegian government formed nine centers of expertise—clusters of world-class enterprise based on strong collaboration between companies, R&D, educational establishments, and the public sector. OCC obtained center of expertise status in June 2007.

    OCC is currently working on a number of initiatives that have been prioritized by members, including the creation of an efficient system for Phase I to Phase III clinical trials. In addition, it wants to work with the Norwegian government on issues like patient reimbursement and tax breaks for life science firms. OCC is also facilitating networking activities, which are so important for small companies to get off the ground.

    Another key issue for OCC is finance. It will work for biotech capital development and seeks to raise the profile of cancer companies in Norway in order to increase investments. “We want more seed funds for life science from the government,” says Einarsson. “We also want foreign investors and money from Norwegians who are interested in life science.”

    Unlike many other European countries, Norway does not have a tradition in research-based pharma, and investments in oil or marine-based industries are far more commonplace. This is beginning to change, however, and Oslo Cancer Cluster wants to capitalize on this newfound interest in biotech.

    The visible culmination of OCC’s aspirations is the building of an Innovation Park, which will include cancer research, biobanking, the national cancer registry, a clinical trials facility, life science companies, and high school science education. The building, due to open in 2012, will be next to the Radium Hospital.

  • Therapeutics

    Meanwhile, OCC members are reporting some exciting developments. Algeta (www.algeta.com) is developing tumor-targeted alpha particle-emitting compounds as cancer therapeutics. Its lead compound, Alpharadin®, contains radium-223 and acts by specifically seeking bony metastases, which take up the radium instead of calcium and are then destroyed by alpha radiation.

    Recent Phase II studies of Alpharadin showed a significant survival benefit in hormone-refractory prostate cancer, and the compound is now poised for a Phase III trial in the same disease, according to Thomas Ramdahl, Ph.D., president and CEO. “The alpha radiation has a short range, and due to radium-223’s specific uptake, the side effect profile of Alpharadin is benign,” Dr. Ramdahl comments. Alpharadin should also be applicable in primary bone tumors and for bony metastases in breast, lung, and kidney cancers.

    DiaGenic (www.diagenic.com), another OCC company, seeks to capture large, fast-growing markets in unmet medical needs with a diagnostics platform that combines gene-expression technology with the traditional blood test. “We’ll be the first company with a blood-based gene-expression test,” says Håkon Sæteroy, executive chairman of the board.

    Initially, the test is being developed for breast cancer where it will be applicable to high-risk groups as an adjuvant to mammography and as a first-line test where mammography is not used.

    The test, a low-density array customized for DiaGenic by Applied Biosystems, is already in research use at pharma companies and will generate its first revenues with its upcoming launch in India, where many women will not undergo mammography.

    DiaGenic is also developing gene expression-based blood tests for CNS applications. It is collaborating with Harvard Medical School under an award from the Michael J. Fox Foundation on a Parkinson’s test. They are also working with the Norwegian Functional Genomics Program on mild cognitive impairment with a view to developing a test for early Alzheimer’s disease.

    A number of OCC member companies are interested in better technologies for delivering cancer drugs. PCI Biotech (www.pcibiotech.no) is developing a light-directed technology. PCI, which stands for photochemical internalization, is applicable to drugs that enter the cell by endocytosis and thereby get trapped in endosomes and are unable to reach their molecular target.

    In PCI, the company’s photosensitizer is administered with the drug and localizes in the membrane of the endosome. Application of laser light then triggers a photochemical reaction that ruptures the endosome and releases the drug to its target. “This technology is applicable to many different classes of molecule,” explains research director Anders Høgset, listing macromolecules, cytotoxics, gene therapy, nanoparticles, and siRNA among PCI’s patented applications.

    PCI Biotech is currently a subsidiary of PhotoCure (www.photocure.com) but will demerge in the summer to pursue its own business development strategy. Currently the company is developing PCI with bleomycin, one of the many anticancer drugs in need of improved delivery.

    Clavis Pharma (www.clavispharma.com) is using its patented lipid vector technology (LVT) to enhance the properties of existing blockbusters—a low-risk strategy for success. LVT involves chemical linking of a fatty acid chain to a small molecule, thereby creating a patentable NCE. “We can improve existing drugs and have a specific technology for doing this,” explains Geir Christian Melen, CEO.

    Clavis’ lead compound, ELACYT™, is the LVT version of cytarabine, the gold standard leukemia drug. It is in Phase II trials for leukemia and solid tumors. CP-4126, the LVT version of Gemzar™ (gemcitabine) is in Phase I for solid tumors and in preclinical phase as an oral dose form. Meanwhile CP-4200, an LVT version of a nondisclosed cancer drug, is in preclinical phase in collaboration with Mount Sinai School of Medicine.

    Epitarget (www.epitarget.com; formerly known as CancerCure) is developing a specialized type of liposome technology. There are already liposome products on the market, mainly for cancer, but they are associated with various side effects. “We are combining liposomes with ultrasound in order to improve targeting,” says Esben A. Nilssen, Ph.D., Epitarget’s CEO.

    Liposomes with a diameter of less than 100 nanometers reach openings in the endothelium of a tumor’s blood supply that are not found in normal tissue.

    “The liposomes accumulate in the tumor and then we use ultrasound to release the drug from them, which gives a high local concentration,” Dr. Nilssen says. The ultrasound component also helps propel the liposomes into tumor tissue and enhances the permeability of the cell so that uptake is more efficient, thus this new form of liposome technology benefits from a triple effect, he adds.

    Other groups have used combinations of heat or light with liposomes, but Epitarget believes that ultrasound gives a more precise effect. The work has involved developing the liposome shell, which is made up of phospholipids, so that it is sonosensitive and stable both on the shelf and in blood.



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