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MEI Pharma Announces Study of Clinical Stage Oral CDK Inhibitor Voruciclib Published in Nature Scientific Reports

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MEI Pharma Announces Study of Clinical Stage Oral CDK Inhibitor Voruciclib Published in Nature Scientific Reports MEI Pharma Announces Study of Clinical Stage Oral CDK Inhibitor Voruciclib Published in Nature Scientific Reports SAN DIEGO, Dec. 21, 2017 /PRNewswire/ -- MEI Pharma, Inc. (Nasdaq: MEIP), an oncology company focused on the clinical development of novel therapies for cancer, today announced that a study of voruciclib, an orally available CDK9 inhibitor, was published in the journal Nature Scientific Reports. Researchers found that voruciclib when combined with the BCL-2 inhibitor Venclexta™ (venetoclax) was capable of inhibiting two master regulators of drug resistance, MCL-1 and BCL-2, and achieved synergistic antitumor efficacy in an aggressive subset of Diffuse Large B-cell Lymphoma (DLBCL). A phase 1 study of voruciclib in relapsed/refractory B-cell malignancies is planned to begin in the first half of 2018. "As an orally available CDK9 inhibitor with a favorable pharmacokinetic profile and the ability to regulate MCL-1 expression, voruciclib is an ideal candidate to test in combination with a BCL-2 inhibitor such as venetoclax in patients with high risk hematological malignancies," said Daniel P. Gold, Ph.D., President and Chief Executive Officer of MEI Pharma. "The fact that overexpression of MCL-1 is a known mechanism of resistance to venetoclax suggests that the combination of MCL-1 and BCL-2 inhibitors may pave the way for a novel treatment strategy for high-risk DLBCL." Approximately 40% of patients with DLBCL do not respond or relapse following standard chemotherapy. The evasion of apoptosis is primarily due to over expression of BCL-2, a pro-survival protein, in response to chemotherapy. The selective inhibition of BCL-2 has been achieved with the BH3 mimetic, venetoclax, resulting in high response rates in certain malignancies. However, exclusive targeting of BCL-2 with venetoclax in relapsed or refractory DLBCL has yielded only a modest 18% response rate with a one-month median progression free survival1. A primary mechanism of resistance to venetoclax is overexpression of MCL-1 which compensates for loss of BCL-2 functionality. The combined targeting of BCL-2 and MCL-1 is a potential treatment strategy for lymphomas that are refractory to standard chemotherapy. Key findings reported in the study: Differentiated structure of voruciclib confers greater selectively for CDK9 compared to other CDK9 inhibitors, with less off-target liability Voruciclib significantly decreased MCL-1 expression in a dose dependent manner at concentrations achievable with doses that appeared to be generally well tolerated in Phase 1 solid tumor studies The combination of voruciclib and venetoclax was more effective than either drug alone, with the best responses in the more aggressive subtypes of DLBCL The published study is available online at https://www.nature.com/articles/s41598-017-18368-w Voruciclib (formerly P1446A) has been tested in more than 70 patients with solid tumors in multiple Phase 1 studies and has been associated with manageable side effects consistent with other drugs in its class, including nausea, vomiting and diarrhea. In pre-clinical studies, voruciclib alone induces cell death in multiple patient- derived chronic lymphocytic leukemia (CLL) samples2. About MEI Pharma MEI Pharma, Inc. (Nasdaq: MEIP) is a San Diego-based oncology company focused on the clinical development of novel therapies for cancer. The Company's portfolio of drug candidates includes pracinostat, an oral HDAC inhibitor that is partnered with Helsinn Healthcare, SA. Pracinostat has been granted Breakthrough Therapy Designation from the U.S. Food and Drug Administration for use in combination with azacitidine for the treatment of patients with newly diagnosed acute myeloid leukemia (AML) who are unfit for intensive chemotherapy. A Phase III study in this patient population is ongoing (NCT03151408). Pracinostat is also being developed in combination with azacitidine in patients with high and very high-risk myelodysplastic syndrome (MDS) (NCT03151304). MEI Pharma's clinical development pipeline also includes ME-401, a highly differentiated oral PI3K delta inhibitor currently in a Phase Ib study (NCT02914938) in patients with relapsed/refractory CLL or follicular lymphoma, and voruciclib, an oral, selective CDK inhibitor shown to suppress MCL1, a known mechanism of resistance to BCL2 inhibitors. The Company is also developing ME-344, a novel mitochondrial inhibitor currently in an investigator-sponsored study (NCT02806817) in combination with bevacizumab for the treatment of HER2-negative breast cancer. Pracinostat, ME-401, voruciclib and ME-344 are investigational agents and are not approved for use in the U.S. For more information, please visit www.meipharma.com. Under U.S. law, a new drug cannot be marketed until it has been investigated in clinical studies and approved by the FDA as being safe and effective for the intended use. Statements included in this press release that are not historical in nature are "forward-looking statements" within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. You should be aware that our actual results could differ materially from those contained in the forward-looking statements, which are based on management's current expectations and are subject to a number of risks and uncertainties, including, but not limited to, our failure to successfully commercialize our product candidates; costs and delays in the development and/or FDA approval, or the failure to obtain such approval, of our product candidates; uncertainties or differences in interpretation in clinical trial results; our inability to maintain or enter into, and the risks resulting from our dependence upon, collaboration or contractual arrangements necessary for the development, manufacture, commercialization, marketing, sales and distribution of any products; competitive factors; our inability to protect our patents or proprietary rights and obtain necessary rights to third party patents and intellectual property to operate our business; our inability to operate our business without infringing the patents and proprietary rights of others; general economic conditions; the failure of any products to gain market acceptance; our inability to obtain any additional required financing; technological changes; government regulation; changes in industry practice; and one-time events. We do not intend to update any of these factors or to publicly announce the results of any revisions to these forward-looking statements. 1J. Clin Oncol. 2017; 35:826-833 2PLoS One. 2015 Nov 25;10(11):e0143685 View original content with multimedia:http://www.prnewswire.com/news-releases/mei-pharma-announces- study-of-clinical-stage-oral-cdk-inhibitor-voruciclib-published-in-nature-scientific-reports-300574438.html SOURCE MEI Pharma, Inc. ORIGINAL NASDAQ-SMALL:MEIP PR Newswire.
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