The most aggressive high-grade glioma is Glioblastoma (GB), a devastating primary brain tumor resistant to conventional therapies, and the second most common cause of death from intracranial disease. The biological characteristics of this tumor are exemplified by prominent proliferation, active invasiveness, and rich angiogenesis. These properties are mainly due to highly deregulated signaling pathways in the tumor.
According to the National Cancer Institute, GB is the most common and malignant form of brain cancer, accounting for over 11,000 new cases in the US every year. Furthermore there is an additional 13,000 new yearly cases in the EU. Following initial treatment, approximately 60% of treated patients will experience tumor progression within one year.
Current intervention for GB – surgery, radiotherapy and chemotherapy – extend overall median survival to only 14.6 months. Many molecular therapies targeting specific pathways, even when used in combination, have failed to improve overall survival or cause a detectable response, likely as a result of tumor heterogeneity arising during disease progression. There is a profound unmet medical need for a new mode of attack that can have a positive impact on the course of disease.
Our lead product, DNX-2401, is an engineered virus capable of selectively and effectively killing a broad range of tumor cells with defects in the retinoblastoma (Rb) pathway. Although we expect that DNX-2401 will demonstrate therapeutic effects in a wide variety of cancers, we are focusing first on Glioblastoma (GB), which accounts for nearly 78% of all high-grade gliomas (HGG) and 53.9% of all gliomas.
DNX-2401 is delivered by direct stereotactic injection into the tumor bed, or following surgical resection, into the walls of the resection cavity to kill residual tumor cells. This product is capable of addressing all recurrences, either surgical or non-surgical, and ultimately newly diagnosed disease with and without surgery.