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May 24, 2011

Centella Licenses Drug Candidate for Hypoxic Tumors

  • Centella Therapeutics entered into a licensing agreement for exclusive rights to Auckland UniServices’ anticancer agent CEN-209. The compound is designed to enhance the effectiveness of radiotherapy and chemotherapy when treating hypoxic solid tumors.

    In addition, Centella plans to develop CEN-109, an investigational PET imaging agent that is designed to identify tumors with hypoxic areas. "CEN-109 has undergone Phase I clinical testing at the University of Pennsylvania and the University of Turku in Finland (under the name 18F-EF5) and is being evaluated in Phase II trials at several clinical centers," says Thorsten Melcher, Ph.D., president of Centella Therapeutics.

    "Our hope is to see CEN-109 approved and labeled for use in identifying patients with hypoxic tumors who would benefit from CEN-209 as an adjunct to their chemotherapy or radiotherapy regimens. We also envision clinicians using CEN-109, if approved, to evaluate the effectiveness of CEN-209 treatments."

    Radiotherapy works by damaging tumor cells' DNA but only in well-oxygenated areas. "Hypoxic tumors are generally resistant to radiotherapy and to chemotherapy, and there is no effective treatment for such tumors today," notes Dr. Melcher.

    CEN-209 is designed to be selectively activated in areas of low oxygen within solid tumors so that it damages the DNA only in these cells, Dr. Melcher explains. "Thus, the two treatment approaches have the potential to complement each other, and CEN-209 is specifically designed to be preferentially used in combination with radiotherapy."

    CEN-209 was created by improving upon tirapazamine (TPZ), another substance that showed early promise in attacking hypoxic cells but did not significantly improve patient outcomes, says professor William Wilson, who identified and characterized CEN-209 with colleagues. TPZ failed partly because it did not penetrate deeply enough into solid tumors to be effective. 

    "TPZ had only a limited ability to reach hypoxic cells, which are generally the cells furthest away from blood vessels," remarks Wilson. "Drs. Kevin Hicks and Frederik Pruijn used sophisticated computer-modeling techniques to validate a predictive model of drug transport within tumors," he added, referring to colleagues at the University of Auckland who collaborated on the research.

    "We believe CEN-209 improves on previous agents in this class in terms of its ability to penetrate tumors, and this is reflected by its improved activity in animals when combined with long or short courses of radiotherapy," notes Wilson.


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