Discovered in our US R&D center, KX-01 and KX-02 oncology drug candidates share two mechanisms of action. They are both non-ATP competitive Src kinase inhibitors and tubulin polymerization inhibitors through binding to a novel site on tubulin heterodimers. In addition, KX02 readily crosses the blood brain barrier and enhances the immune system in the brain for attacking brain tumors as a third mechanism of action. Importantly, the multi-mechanisms of action for KX01 and KX02 provide broader, and more sustained, anti-tumor efficacy than would be provided by Src kinase inhibition alone. This is in effect incorporating a number of the advantages of oncology drug combination therapy into single drugs.
KX01 (KX2-391): An Ointment Formulation
The topical ointment formulation of KX01 is expected to be useful in a variety of cancer and pre-cancer related skin ailments. Clinical data in the US indicate our ointment is very likely to be a promising product for the treatment of actinic keratosis as compared to current therapy. Clinical evaluation for its utility in treating psoriasis has also begun.
KX01 (KX2-391): An Oral Formulation
KX01 as a small molecule, orally active and highly selective inhibitor of Src tyrosine kinase signaling and tubulin polymerization has generated positive signals in a US acute myelogenous leukemia study and in certain solid tumors. KX01 promotes the induction of p53, G2/M arrest of proliferating cell populations and subsequent apoptosis via the stimulation of Caspase-3 and PARP cleavage. Since KX01 is readily absorbed orally it allows multi-day dosing regimens to optimize the efficacy vs toxicity that are not practical with IV tubulin targeting drugs such as vincristine and vinblastine. We are currently exploring its best application in solid and liquid tumors.
KX02 (KX2-361): An Oral Formulation
KX02 is a small molecule orally active inhibitor against a broad panel of central nervous system tumor cell lines, including glioblastoma multiforme (GBM), the most common and aggressive brain cancer. KX02 is effective against GBM tumor cells that are resistant to Temozolomide (T98G), the most widely used chemotherapy for the treatment of GBM. KX02 readily, and completely, crosses the blood-brain barrier to provide drug concentrations in the brain that are higher than that in the plasma. Even more promising is the ability of KX02 to activate the immune system to attack GBM cells in the brain thereby producing cures in mouse GBM models containing an intact immune system.