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Nventa’s lead initiative is the development of HspE7, a proprietary CoVal™ fusion protein, for the treatment of a variety of serious diseases caused by the human papillomavirus (HPV). HspE7 is an investigational therapeutic vaccine, also known as an immunotherapeutic, made using recombinant DNA technology that covalently fuses a heat shock protein (Hsp) to an HPV E7 viral protein to form one CoVal™ therapeutic protein. The E7 viral protein is often poorly recognized by the human immune system. By combining the Hsp with E7, an E7-specific immune response can be achieved. HspE7 works by efficiently delivering the E7 antigen to dendritic cells, which have a natural affinity for Hsp. Dendritic cells are known to be the most potent cells in the body for triggering immune responses. Dendritic cells are a type of white blood cell that educates other white blood cells, called T cells, to seek out and destroy diseased cells in the body infected by viruses or cancer. Dendritic cells work by binding, engulfing and processing proteins called antigens that are expressed by viruses and cancer cells into small fragments. The dendritic cells then present these fragments on their surface to program T cells to recognize these fragments as foreign and harmful. Once T cells identify the fragments as foreign, they rapidly multiply and roam the body to target and kill infected cells that express the antigens. These types of T cells are called killer T cells.  Coupling E7 to Hsp takes advantage of the Hsp receptors that dendritic cells express on their surface to introduce E7, as part of a larger fusion protein, into the dendritic cells. The introduction of the fusion protein appears to allow the dendritic cells to process E7 and produce specific antigens to promote a killer T cell response against infected cells that express the E7 protein.
In preclinical studies conducted using a tumor animal model, administration of HspE7 has been shown to prevent the growth of and cause the destruction of tumors that express the HPV E7 protein. According to Nventa research, neither the E7 antigen nor the Hsp alone, nor a mixture of the two, is effective. Download a PDF of the HPV poster Nventa originally advanced HspE7 on its own into multiple Phase 2 clinical trials with positive results generated in patients with cervical dysplasia, genital warts and in patients co-infected with both the HPV and HIV viruses. However, upon further investigation, the Company discovered that by using an adjuvant (a substance meant to boost the effect of a vaccine), HspE7 potency could be increased dramatically. As a result, Nventa is now pursuing clinical development of a new formulation of HspE7 incorporating the adjuvant Poly-ICLC. Clinical development of HspE7 is initially focusing on cervical dysplasia, a precursor to cervical cancer; further development in recurrent respiratory papillomatosis (RRP) (an indication for which Nventa received both Orphan Drug designation and Fast Track status from the FDA) and genital warts (GW) is likely. Nventa plans to solidify its clinical plan during 2007 once determining which indication(s) could be the most efficient route to regulatory approval of HspE7. |
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HspE7 Executive Summary (PDF)