RP-1664: Our Polo-like Kinase 4 (PLK4) preclinical program.

We are developing a first-in-class, highly selective, oral 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. Elevated TRIM37 is a feature found across a range of solid tumors and in approximately 80% of high-grade neuroblastoma.

We reported comprehensive preclinical data for RP-1664 in November 2023, including deep tumor growth inhibition and regressions in multiple TRIM37-high solid tumor or neuroblastoma xenograft models. The preclinical in vivo animal model evaluations were performed both internally and in collaboration with Children’s Hospital of Philadelphia. In February 2024, we dosed the first patient in the LIONS (PLK4 Inhibitor in Advanced Solid Tumors) clinical trial, a multicenter, open-label Phase 1 clinical trial to investigate safety, pharmacokinetics, pharmacodynamics, and the preliminary efficacy of RP-1664. After evaluating safety in adult patients with recurrent solid tumors in the LIONS clinical trial, we expect to move into a Phase 1/2 clinical trial in high risk, recurrent pediatric neuroblastoma, in which children have limited treatment options and high prevalence of TRIM37-altered tumors.