AUM302 is a first-in-class oral kinase inhibitor rationally designed to uniquely combine pan-PIM kinase, pan-PI3K and mTOR inhibition in a single agent. It has potent efficacy, good tolerability and favorable drug properties.
The complexity of the PI3K/AKT/mTOR signaling network involves numerous feedback loops, extensive crosstalk nodes with other signaling pathways and compensatory pathways, providing ample opportunities for circumventing the effects of PI3K inhibition. It is one of the most frequently dysregulated pathways in cancer, and often considered to be the very hallmark of cancer.
Oncogenic activation of the PI3K pathway promotes cell growth, survival, and resistance to both chemotherapy and radiotherapy. Critically, PI3K pathway activation often occurs alongside pro-tumorigenic aberrations in other signaling networks, thereby enabling a tumor cell to resist the effects of PI3K inhibition and/or to readily develop such resistance.
Cancer resistance to PI3K inhibitor therapy can be in part mediated by increases in PIM kinases as well as through the mTORC1/Mcl-1 pathway. Pan-PIM inhibition results in the interruption of the G1/S phase cell cycle transition, thereby causing cell cycle arrest and inducing apoptosis in cells that overexpress PIMs. Inhibition of mTOR can circumvent mTOR mediated PI3K inhibitor failure. Consequently, studies of combinations of PI3K/mTOR, PI3K/AKT and PI3K/PIM inhibitors have been proposed and are being actively explored.
AUM302 is a unique multi-targeted cancer therapeutic that targets not only PI3K, but also key resistance mechanisms such as PIM and mTOR. AUM302 is a single molecule therapeutic that has been optimized to inhibit these key pathways.
AUM Biosciences is building a rationally designed drug pipeline selected not only for individual agent efficacy but also for an intra-pipeline combinatorial strategy. AUM302 is refinement of this strategy in that it is rationally designed to not only be a pan-PI3K inhibitor, but also to be a pan-PIM inhibitor and an mTOR inhibitor. This multi-targeting ability has been engineered into a single molecule that has the ability to inhibit multiple key intracellular pathways, increasing its ability to inhibit cancer cell growth and prevent resistance emergence. Studies have also indicated that amplification of both MYC and eIF4E can also mediate resistance to PI3K/mTOR inhibitors. A combination of AUM001 with AUM302 has the potential to address yet another key resistance, and in the case of MYC, thus far undruggable pathway.
AUM302 is in late pre-clinical development and undergoing IND-enabling studies.
For more information about the AUM302 program, interested scientists and physicians can contact AUM Biosciences at firstname.lastname@example.org.