On June 1, 2019 MEI Pharma, Inc. (NASDAQ: MEIP), a late-stage pharmaceutical company focused on advancing potential new therapies for cancer, reported data presented at ASCO (Free ASCO Whitepaper) 2019 from an investigator-initiated study of investigational ME-344 in combination with bevacizumab (marketed as Avastin) in patients with early HER2-negative breast cancer (Press release, MEI Pharma, JUN 1, 2019, View Source [SID1234536756]). This study demonstrated proof of biologic anti-tumor activity as measured by a statistically significant reduction in Ki67, a measure of cell proliferation that is highly correlated with tumor response, in the group of patients treated with ME-344 compared to an increase in the group receiving saline.

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"Data from this clinical study of ME-344 in combination with bevacizumab represents a potential novel approach to disrupting tumor metabolism and limiting tumor proliferation by inhibiting the heightened energy production necessary for cell division and cancer growth," stated the study principal investigator, Miguel Quintela-Fandino, M.D., Ph.D., Director of the Clinical Research Program, Centro Nacional De Investigaciones Oncologicas, Madrid, Spain. "These results offer evidence for the biologic antitumor activity of ME-344 in certain metabolic contexts and support further exploration of the mitochondrial inhibitor ME-344 in a therapeutic role, providing a potential novel mechanism that may improve patient outcomes in combination with antiangiogenic therapeutics such as bevacizumab."

The ME-344 ASCO (Free ASCO Whitepaper) 2018 poster can be accessed on the MEI Pharma website.

ME-344 Clinical Data
The clinical study was a multicenter, investigator-initiated, randomized, open-label trial evaluating ME-344 in a total of 42 patients with early HER2-negative breast cancer in combination with the vascular endothelial growth factor inhibitor bevacizumab. Patients were randomized one-to-one to either ME-344 plus bevacizumab or saline plus bevacizumab.

The primary objective of the study was to show proof of ME-344 biologic activity as measured by Ki67 reductions from day 0 to 28 compared to placebo. Secondary objectives included determining whether ME-344 biologic activity correlates with vascular normalization. The data demonstrate significant biologic activity in the ME-344 treatment group:

In ME-344 treated patients, mean absolute Ki67 decreases were 13.3 compared to an increase of 1.1 in the bevacizumab monotherapy group (P=0.01).
In ME-344 treated patients, mean relative Ki67 decreases were 23% compared to an increase of 186% in the bevacizumab monotherapy group (P < 0.01).
The mean relative Ki67 reduction in patients experiencing vascular normalization in the ME-344 treated patients was 33%, compared to an increase of 11.8% in normalized patients from the bevacizumab monotherapy group (P=0.09). Approximately one-third of patients in each arm had vascular normalization.
Treatment was generally well tolerated; two Grade 3 adverse events of high blood pressure were reported, 1 in each arm, and deemed related to bevacizumab.

About ME-344
ME-344 is a novel, tumor selective, isoflavone-derived mitochondrial inhibitor drug candidate. It directly targets the OXPHOS complex 1, a pathway involved in the production of adenosine triphosphate, or ATP, in the mitochondria. Treatment of tumor cells with ME-344 results in a rapid loss of ATP and cancer cell death. ME-344 demonstrated evidence of single-agent activity against refractory solid tumors in a Phase I study, and in preclinical studies, tumor cells treated with ME-344 resulted in a rapid loss of ATP and cancer cell death.

In addition to single-agent activity, ME-344 may also have potential in combination with antiangiogenic therapeutics. While antiangiogenics reduce the rate of glycolysis in tumors as a mechanism to block growth, tumor metabolism often shifts to mitochondrial metabolism to continue energy production to support continued tumor proliferation. In such cases of tumor plasticity in the presence of treatment with antiangiogenics, targeting the alternative metabolic source with ME-344 may open an important therapeutic opportunity.