MEI Pharma's Mitochondrial Inhibitor ME-344 Shows Enhanced Anti-Tumor Activity in Combination with Tyrosine-Kinase Inhibitor in Pre-Clinical Studies

SAN DIEGO, May 4, 2015 /PRNewswire/ -- MEI Pharma, Inc. (Nasdaq: MEIP), an oncology company focused on the clinical development of novel therapies for cancer, today announced new pre-clinical data showing mitochondria-specific effects of the Company's investigational drug candidate ME-344 in cancer cells, including significantly enhanced anti-tumor activity when combined with a tyrosine-kinase inhibitor (TKI). In addition, a recently published study found ME-344 to be a potent inhibitor of mitochondrial oxidative phosphorylation (OXPHOS) complex I, a direct molecular target.

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"We continue to be very excited by the potential of this novel mitochondrial inhibitor," said Daniel P. Gold, Ph.D., President and Chief Executive Officer of MEI Pharma. "ME-344 has demonstrated broad and potent anti-tumor activity in a number of pre-clinical studies, followed by promising single-agent activity in the clinic. Now a body of data is emerging that show compelling anti-cancer effects when combining ME-344 with anti-angiogenic agents, such as TKIs, to inhibit both mitochondrial and glycolytic metabolism. These new data will help to direct future studies of ME-344 as we near completion of our Phase Ib study in small cell lung and ovarian cancers."

In a paper published in the most recent issue of American Journal of Cancer Research¹, the Company's collaborators at the MIMR-PHI Institute of Medical Research in Melbourne identified mitochondrial OXPHOS complex I as a direct molecular target of ME-344, its inhibition causing an immediate reduction of mitochondrial oxygen consumption. This important finding provides new understanding of how ME-344 induces cell death by disrupting mitochondrial metabolism. A copy of the paper is available at www.meipharma.com.

To gain further insight into its mechanism of action, researchers at the Medical University of South Carolina in Charleston compared the activity of ME-344 in sensitive and naturally resistant lung cancer cell lines. In a dose dependent manner, ME-344 caused instantaneous and pronounced inhibition of oxygen consumption rates in drug-sensitive lung cancer cells, but significantly less in drug-resistant cells. Notably, drug resistance correlated with higher glycolytic metabolism in these cells.

Using a well-characterized spontaneous breast tumor model, researchers at the Spanish National Cancer Research Centre in Madrid found that chronic treatment with the small molecule TKI nintedanib (formerly BIBF 1120) significantly diminished tumor cell glycolysis, however the growing tumor shifted to reliance on mitochondrial metabolism as its primary energy source. Subsequently, tumors primed by treatment with nintedanib showed significantly enhanced sensitivity to the mitochondrial inhibitor ME-344, with synergistic anti-tumor activity.

These findings are presented in a poster, entitled "ME-344, a novel isoflavone with activity as a mitochondrial oxygenase inhibitor," which is available at www.meipharma.com. An abstract of the presentation can be found on the American Association for Cancer Research (AACR) website at aacr.org.

Results from First-in-Human Study Published in Cancer

Results from MEI Pharma's Phase I study of ME-344 were recently published in the April 1, 2015 issue of Cancer². The study showed evidence of single-agent activity in patients with refractory solid tumors, including five patients who experienced progression-free survival that was at least twice the duration of their last prior treatment. Notably, one patient with small cell lung cancer achieved a confirmed partial response and remained on study for 104 weeks. ME-344 was generally well tolerated in the study at doses equal to or less than 10 mg/kg delivered on a weekly schedule for extended durations. Treatment-related adverse events included nausea, dizziness and fatigue. Dose limiting toxicities were observed at both the 15 and 20 mg/kg dose levels, consisting primarily of Grade 3 peripheral neuropathy.

In May 2014, the Company initiated a Phase Ib clinical trial of ME-344 in combination with topotecan (marketed as Hycamtin^®), a drug approved by the U.S. Food and Drug Administration for the treatment of small cell lung, ovarian and cervical cancers. In October 2014, the first patient was dosed in the cohort-expansion stage of the study after the initial stage confirmed the maximum tolerated dose of ME-344 at 10 mg/kg in combination with 4 mg/m² of topotecan. The combination of ME-344 and topotecan has been generally well tolerated in the study; the most frequent side effects are fatigue and gastrointestinal disturbances. The study is currently enrolling an additional 40 patients into two cohorts, locally advanced or metastatic small cell lung and ovarian cancer, at nine sites in the U.S. and U.K. The Company expects to present data from the ovarian cancer cohort at a scientific meeting during the fourth quarter of 2015.

MEI Pharma owns exclusive worldwide rights to all of its drug candidates, including ME-344.

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, a potential best-in-class, oral HDAC inhibitor currently being developed for advanced hematologic diseases, such as myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Full data from the Company's Phase II study of Pracinostat in combination with azacitidine in elderly patients with newly diagnosed AML are expected in June 2015. MEI Pharma is also developing ME-344, a mitochondrial inhibitor currently in a Phase Ib study in combination with topotecan in patients with small cell lung or ovarian cancer who failed initial therapy. In addition, the Company expects to initiate a first-in-human study of PWT143, a highly selective PI3K delta inhibitor, in June 2015. 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 study 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.

¹ Am J Cancer Res 2015;5(2):689-701
² Cancer. 2015 Apr 1;121(7):1056-63

SOURCE MEI Pharma, Inc.

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