LA JOLLA, Calif., Dec. 01, 2016 (GLOBE NEWSWIRE) -- Kura Oncology, Inc. (Nasdaq:KURA), a clinical stage biopharmaceutical company, today presented preclinical data highlighting the identification and characterization of KO-947, its development candidate targeting ERK1/2 kinases. The company has also presented preclinical data relating to the identification and optimization of potent and selective inhibitors of the menin-MLL interaction. Both presentations took place at the EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics (EORTC) in Munich, Germany.
“We are excited to present preclinical data from these two innovative programs at EORTC, both of which showed compelling activity in preclinical models of cancer,” said Yi Liu, Ph.D., Chief Scientific Officer. “Looking forward, we anticipate nominating a development candidate for our menin-MLL program by the end of 2016, and initiating a Phase 1 clinical trial for KO-947 in the first half of 2017.”
KO-947 - A potent and selective inhibitor of ERK1/2 kinases
The RAS/RAF/MEK pathway is estimated to be activated in more than 30% of human cancers, including cancers arising from mutations in KRAS, NRAS and BRAF. Although inhibitors of both BRAF and MEK have been approved for treatment of melanoma, acquired resistance to these inhibitors has been documented both in preclinical and clinical samples due to reactivation of ERK1/2 kinases.
In preclinical studies presented today at EORTC, KO-947 showed potent inhibition of ERK signaling pathways and proliferation of tumor cells exhibiting dysregulation of MAPK pathway, including mutations in BRAF, NRAS or KRAS. KO-947 also inhibits MAPK signaling and cell proliferation in preclinical models that are resistant to BRAF and MEK inhibitors. Results obtained from screening a large panel of PDX models demonstrate that KO-947 induces tumor regressions in BRAF or RAS mutated tumor models as well as in tumor models lacking BRAF/RAS mutations but characterized by other dysregulation of the MAPK pathway.
KO-947 appears to be differentiated from other published ERK inhibitors by an extended residence time and prolonged pathway inhibition in vitro and in vivo. The data further suggest that the drug properties of KO-947 may allow Kura to maximize the therapeutic window with flexible administration routes and schedules, including intermittent dosing.
Inhibitors of the Menin-MLL Interaction
Chromosomal translocations that affect the mixed lineage leukemia (MLL) gene result in aggressive acute myeloid and lymphoid leukemias that are often resistant to standard chemotherapy. Approximately 5-10% of acute leukemias in adults, and 70% of acute leukemias in infants, are characterized by tumors with abnormal MLL fusions. MLL fusion proteins require menin for leukemogenic activity and selective disruption of the menin-MLL interaction represents a potential therapeutic approach for the treatment of acute leukemias with MLL rearrangements.
In preclinical studies presented at EORTC, inhibitors of the menin-MLL interaction showed potent inhibition of the proliferation of MLL leukemic cells. Inhibitors of the menin-MLL interaction displayed a greater than 50-fold reduction in potency in non-MLL-fusion leukemia cell lines and induced regression in a MV4:11 mouse xenograft model. The data show that the anti-tumor activity of menin-MLL inhibitors correlates with target engagement in tumors as well as inhibition of expression of downstream genes under the regulation of the fusion protein. Moreover, the inhibitors demonstrated potent efficacy in subcutaneous and disseminated models of MLL-fusion leukemias.
Both of the posters presented at EORTC can be found on Kura’s website in the Scientific Presentations and Papers section or by clicking here.
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 molecules 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 preclinical pipeline includes KO-947, an ERK inhibitor, and a menin-MLL program. For additional information about Kura Oncology, please visit the company’s website at www.kuraoncology.com.
Forward Looking Statements
This news release contains certain forward-looking statements that involve risks and uncertainties that could cause actual results to be materially different from historical results or from any future results expressed or implied by such forward-looking statements. Such forward-looking statements include statements regarding, among other things, the potential utility KO-947 and Kura Oncology’s other compounds and product candidates, the conduct, results and timing of preclinical studies and clinical trials and plans regarding future research and development. Factors that may cause actual results to differ materially include the risk that compounds that appeared promising in early research or clinical trials do not demonstrate safety and/or efficacy in later preclinical studies or clinical trials, the risk that Kura Oncology may not obtain approval to market its product candidates, uncertainties associated with regulatory filings and applications, the risks associated with reliance on outside financing to meet capital requirements, and the risks associated with reliance on collaborative partners for further research, clinical trials, development and commercialization of product candidates. You are urged to consider statements that include the words “may,” “will,” “would,” “could,” “should,” “believes,” “estimates,” “projects,” “promise,” “potential,” “expects,” “plans,” “anticipates,” “intends,” “continues,” “designed,” “goal,” or the negative of those words or other comparable words to be uncertain and forward-looking. For a further list and description of the risks and uncertainties the Company faces, please refer to the Company's periodic and other filings with the Securities and Exchange Commission, which are available at www.sec.gov. Such forward-looking statements are current only as of the date they are made, and Kura Oncology assumes no obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.
Last updated on: 02/12/2016
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