RP-1664 PLK4 Inhibitor
RP-1664: Our Polo-like Kinase 4 (PLK4) preclinical program.
We are developing a highly selective small molecule inhibitor of Polo-like kinase 4, or PLK4, a SL target associated with TRIM37 overexpression. PLK4 regulates centriole production. Cells with high levels of TRIM37 are reliant on centrioles for successful cell division. When PLK4 is inhibited, hindering centrioles, these TRIM37-high cells cannot successfully divide, resulting in synthetic lethality.
PLK4 inhibition is one of the most anticipated new targets in recent years.
Preclinical studies have demonstrated that RP-1664 drives potent synthetic lethality in TRIM37-high tumor models, both in vitro and in vivo. Elevated TRIM37 is a feature found across a range of solid tumors, including in nearly all high-grade neuroblastomas as well as in non-small cell lung cancer, breast cancer, and gastric cancer.
We anticipate advancing RP-1664 into the clinic in the first half of 2024.