On June 4, 2018 MEI Pharma, Inc. (Nasdaq: MEIP), a pharmaceutical company focused on leveraging its extensive development and oncology expertise to identify and advance new therapies for cancer, reported that data presented at ASCO (Free ASCO Whitepaper) 2018 from an investigator-initiated study of ME-344 in patients with HER2 negative breast cancer demonstrate evidence of inhibition of tumor proliferation as measured by Ki-67 reductions (Press release, MEI Pharma, JUN 4, 2018, View Source [SID1234527129]). These interim data are consistent with preclinical results indicating ME-344’s potential to reverse resistance to anti-angiogenic therapy, thereby warranting the continuation of the ongoing study.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
"The goal of this study is to gain a better understanding of the escape pathways that may be utilized by tumors against antiangiogenic therapeutics. The interim results from this study suggest that there may be an important therapeutic role for mitochondrial inhibitors like ME-344, providing a potential novel mechanism to improve patient outcomes in combination with antiangiogenic therapeutics," 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.
"We are looking forward to continuing our work with Dr. Quintela-Fandino as we further elucidate the opportunity to advance ME-344 as part of a novel approach for the treatment of cancer," said Daniel P. Gold, Ph.D., president and chief executive officer of MEI Pharma.
The ME-401 ASCO (Free ASCO Whitepaper) 2018 poster can be accessed on the MEI Pharma website.
ME-344 Clinical Data
The ongoing study is a multicenter, investigator-initiated, randomized, open-label, clinical trial evaluating ME-344 in a total of up to 40 patients with HER2-negative breast cancer in combination with the vascular endothelial growth factor inhibitor bevacizumab (marketed as Avastin). Patients are randomized one-to-one to either ME-344 plus Avastin or saline plus Avastin. The interim data review was predefined to take place after 20 patients were randomized.
The primary efficacy endpoint is inhibition of cell proliferation as measured by Ki-67 reductions. Mean absolute (relative) Ki67 decreases were 5.13 (29%) and 1.2 (9%) in the active versus control arms (P=0.06). Patients with standardized uptake values via PET scan ≥ 10% experienced an absolute average Ki67 decrease of 16.6 vs. 2.3 in the active versus control arms (P=0.19). Treatment was generally well tolerated; two Grade 3 adverse events (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.