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MVA 5T4 consists of the highly attenuated modified Vaccinia Ankara virus containing the gene encoding the human TAA 5T4 under regulatory controlled of a modified controller, mH5. Ninety percent or more of RCCs overexpress the 5T4 antigen. A series of clinical trials were conducted to evaluate the effectiveness of MVA 5T4 as a single agent or in combination with Interleukin -2 or Interferon Alpha 2B. Endpoints included safety, immunogencity and indications of clinical benefit (tumor responses). A total of 33 patients received MVA 5T4 alone or in combination.

MVA 5T4 was safe and well tolerated in the context of both cytokines with no MVA 5T4 serious related AEs. Antibody responses were observed in >90% of patients irrespective of treatment group (table below), suggesting that neither IL2 nor IFN enhance the significant immune response to MVA 5T4 alone. Further immunological analysis including cellular responses are ongoing.

Although comparable antibody response were observed in papillary and clear cell histotypes, clear cell patients appeared to be more likely to respond in terms of clinical benefit parameters, to be presented. Of note is that preliminary analysis of clear cell patients suggests a relationship between the anti-5T4 immune response and tumor response. This relationship is specific to 5T4 and not simply a measure of immunocompetence (no correlation with anti-MVA response). With the immunological potency and encouraging clinical activity establish the future research will focus on the phase 3 randomized, double-blind, placebo controlled parallel group study to investigate whether MVA 5T4, added to first line standard of care therapy, prolongs the survival of patients with locally advanced or metastatic clear cell renal adenocarcinoma as well as further clinical research studies that seek to further optimize MVA 5T4 potency.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA