DFN-529

DFN-529 is a novel allosteric inhibitor of a phosphoinositide 3-kinase (PI3K)/AKT/mechanistic target of rapamycin (mTOR) pathway inhibitor that interferes with the pathway through both mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2) dissociation. This is a key pathway involved in the control of cell-cycle signalling, and directly related to cellular proliferation and cancer.

DFN-529 has received Orphan Drug Designation from the US Food and Drug Administration for treatment of glioblastoma multiforme (GBM), which is the most common form of brain cancer. DFN-529 inhibits cell growth leading to death of various cancer cell types grown in vitro. In animal tumor models where the PI3K/AKT/mTOR pathway is abnormally activated, DFN-529 reduces tumor growth and its mechanism is synergistic with radiation therapy, chemotherapy, and hormonal therapy through inhibition of the PI3K/AKT/mTOR pathway. Furthermore, the compound has shown antiangiogenic activity in several animal models, including GBM. Current inhibitors of this pathway have primarily targeted mTORC1, but have shown limited clinical efficacy. Inhibitors of mTORC1 and mTORC2, such as DFN-529, may therefore have the potential to overcome the deficiencies found in targeting only mTORC1.

DFN-529 has been studied in two completed Phase 1 clinical trials for age-related macular degeneration, and has undergone preclinical evaluation for use in treating GBM. The compound been demonstrated to be orally bioavailable and capable of crossing the blood-brain barrier. We are currently exploring alternatives to best capitalize upon the value of DFN-529 and our related intellectual property.

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