KO-947 is a potent and selective inhibitor of ERK1/2 kinases, which are critical components of the MAPK pathway. Aberrant signaling caused by mutations or dysregulation of the MAPK pathway are frequent contributors to the development of cancer and are associated with numerous tumor types, including lung, colorectal and pancreatic adenocarcinomas and squamous cell carcinomas. Although small molecule inhibitors of BRAF and MEK have demonstrated clinical activity in selected patients, duration of response has been limited, and resistance is often associated with reactivation of the MAPK signaling pathway. In preclinical studies presented at AACR, KO-947 demonstrated prolonged inhibition of the MAPK pathway. Durable tumor regression was observed in preclinical cell line and patient derived xenograft models, including KRAS- and BRAF-mutant adenocarcinomas and squamous cell carcinomas lacking BRAF/RAS mutations, when KO-947 was administered on schedules ranging from daily to once weekly. Kura anticipates initiating a Phase 1 clinical trial for KO-947 in 1H 2017.
KO-539 is a potent and selective inhibitor of the interaction between the menin protein and the MLL fusion proteins, which characterize MLL leukemias. MLL-rearranged leukemia patients typically have a poor prognosis with a 5-year survival rate estimated to be 40%. As the leukemogenic activity of MLL fusion proteins has been shown to be dependent on their direct interaction with menin, the development of small molecules that block the menin-MLL interaction is a promising therapeutic strategy for the treatment of this disease. In preclinical studies presented at AACR, KO-539 demonstrated robust, sustained tumor regressions in multiple aggressive models of MLL-rearranged leukemias that correlated with modulation of target gene expression. KO-539 has been nominated as a development candidate, and further efforts are currently underway to assess potential utility of menin-MLL inhibitors in additional hematological malignancies and solid tumor indications.
About Kura Oncology
Kura Oncology is a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer. The company’s pipeline consists of small molecule drug candidates that target cancer signaling pathways where there is a strong scientific and clinical rationale to improve outcomes by identifying those patients most likely to benefit from treatment. Kura Oncology’s lead drug candidate is tipifarnib, a farnesyl transferase inhibitor, which is currently being studied in multiple Phase 2 clinical trials. The pipeline includes KO-947, an ERK inhibitor, and KO-539, an inhibitor of the menin-MLL protein-protein interaction. For additional information about Kura Oncology, please visit the company’s website at www.kuraoncology.com.