“Roughly half of patients with relapsed or refractory NPM1-mutant AML have co-occurring FLT3 mutations, and the prognosis for these patients is particularly poor,” said Stephen Dale, M.D., Chief Medical Officer of Kura Oncology. “Given the potential best-in-class safety and tolerability profile as well as the robust monotherapy activity observed in our Phase 1 study of ziftomenib, we believe an all-oral combination of ziftomenib and gilteritinib may provide an attractive treatment option for these patients.” Preclinical data for menin inhibitors in combination with multiple FLT3 inhibitorsFLT3 inhibitors demonstrate strong synergistic effects compared to either single agent alone. Currently there are no other actively recruiting clinical trials evaluating the combination of a menin inhibitor with a FLT3 inhibitorFLT3 inhibitor for the treatment of AML. AML is the most common acute leukemia in adults and begins when the bone marrow makes abnormal myeloblasts (white blood cells), red blood cells or platelets. Despite the many available treatments for AML, prognosis for patients remains poor and a high unmet need remains. The menin pathway is considered a driver for multiple genetic alterations of the disease, of which NPM1 mutations are among the most common, representing approximately 30% of AML cases and KMT2A rearrangements represent approximately 5-10% of AML cases. While patients with NPM1-m AML have high response rates to frontline therapy, relapse rates are high and survival outcomes are poor, with only 30% overall survival at 12 months in the R/R setting. Additionally, NPM1 mutations frequently occur with co-mutations in other disease-associated genes, including FLT3, DNMT3A and IDH1/2, with prognosis heavily influenced by the presence of co-occurring mutations. Adult patients with NPM1-m AML and select co-mutations and/or R/R disease have a poor prognosis, with median overall survival of only approximately 7.8 months in 2nd line, 5.3 months in 3rd line and 3.5 months following the 4th line1. Adult patients with KMT2A-r AML have a poor prognosis with high rates of resistance and relapse following standard of care, with median overall survival for this patient population of only 6 months following 2nd line and 2.4 months following 3rd line2. No FDA-approved therapies targeting NPM1-m and KMT2A-r AML currently exist. Ziftomenib is a novel, once-daily, oral investigational drug candidate targeting the menin-KMT2A/MLL protein-protein interaction for treatment of genetically defined AML patients with high unmet need. Ziftomenib inhibits the KMT2A/MLL protein complex and exhibits downstream effects on HOXA9/MEIS1 expression and potent anti-leukemic activity in genetically defined preclinical models of AML. Ziftomenib has received Orphan Drug Designation from the U.S. Food and Drug Administration for the treatment of AML. Additional information about clinical trials for ziftomenib can be found at kuraoncology.com/clinical-trials/#ziftomenib. 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 efficacy, safety and therapeutic potential of ziftomenib, potential benefits of combining ziftomenib with appropriate standards of care, and progress and expected timing of the ziftomenib program and clinical trials. 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 may not obtain approval to market its product candidates, uncertainties associated with performing clinical trials, regulatory filings, applications and other interactions with regulatory bodies, risks associated with reliance on third parties to successfully conduct clinical trials, risks associated with reliance on outside financing to meet capital requirements, and other risks associated with the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such drugs. 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 assumes no obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise. Executive Vice President, Investor Relations &
Associate Director, Corporate Communications &
alexandra@kuraoncology.com
1 Issa GC, et al. Blood Adv. 2023;7(6):933-42.
2 Issa GC, et al. Blood Cancer J. 2021;11(9):162.