MEI Pharma, Inc. (NASDAQ: MEIP), a clinical-stage pharmaceutical company focused on advancing new therapies for cancer, today announced the dosing of the first patient in a Phase 1b study evaluating ME-344 in combination with bevacizumab (AVASTIN®) in patients with previously treated metastatic colorectal cancer.

ME-344 is a novel mitochondrial inhibitor targeting energy production through the OXPHOS pathway, which is important for supporting tumor cell survival and proliferation for many forms of cancer, including colorectal cancer. Bevacizumab, a vascular endothelial growth factor (VEGF) inhibitor, and other antiangiogenics, increase reliance on mitochondrial energy production, thereby providing an important opportunity to evaluate a combination with a mitochondrial inhibitor like ME-344 to inhibit energy production in tumor cells and induce an antitumor effect.

“As one of the most commonly diagnosed cancers, and a leading cause of cancer-related deaths in both men and women in the United States, there is a high medical need for new therapies to treat colorectal cancer, particularly for patients who have failed standard therapy and have metastatic disease,” stated Dr Howard Hochster, Distinguished Professor, and Director, GI Oncology, Rutgers Cancer Institute. “This clinical study presents an important opportunity to evaluate a novel approach to treatment with the potential to bring improved benefit to patients. This target is quite unlike other treatments for colorectal cancer, and will be studied by investigators at the Rutgers Cancer Institute Metabolomics Center of Excellence in conjunction with the trial. We are excited to join with our colleagues nationally in the Academic GI Cancer Consortium (AGICC) to investigate this promising agent.”

“We are excited to continue to pioneer the evaluation of mitochondrial inhibition as a promising approach to treat solid tumors with the initiation of this innovative study evaluating ME-344, our mitochondrial inhibitor, in combination with bevacizumab in patients with colorectal cancer who progressed after standard therapies,” said Richard Ghalie, M.D., chief medical officer, of MEI Pharma. “With the current study, we look forward to the opportunity to build on both mechanistic and efficacy data from earlier pre-clinical and clinical studies demonstrating the anti-tumor activity of ME-344 in combination with bevacizumab.”

The Company anticipates announcing safety and efficacy data from the first cohort of 20 ME-344 patients in the first half of 2024.

About the Phase 1b Study

The Phase 1b study is evaluating ME-344 plus bevacizumab across two cohorts in patients with metastatic colorectal cancer after failure of standard therapies. Twenty patients will be enrolled in the first cohort and receive ME-344 at 10 mg/kg once weekly in combination with bevacizumab every two weeks. If the rate of non-progression in Cohort 1 reaches a predetermined progression free survival threshold, Cohort 2 will enroll an additional 20 patients who will receive ME-344 every 2 weeks to match bevacizumab infusion frequency. Patients will be treated until disease progression or intolerability. The primary endpoint of the study is progression free survival. Secondary endpoints include overall response rate, duration of response, overall survival and safety.

About ME-344

ME-344 is a novel mitochondrial inhibitor drug candidate that has demonstrated tumor selective activity in pre-clinical studies. It targets the OXPHOS pathway involved in the production of adenosine triphosphate, or ATP. Energy supplied in the form of ATP fuels tumor metabolism supporting cell division and growth. By disrupting the production of ATP, ME-344 has been shown pre-clinically to induce cancer cell death through the induction of DNA fragmentation and through a process known as destructive autophagy, whereby a cell consumes itself. ME-344 has also demonstrated evidence of antitumor activity in preclinical and clinical studies.

The two major sources of ATP are the mitochondria and glycolysis, a process that breaks down glucose. It is understood that anti-angiogenics, like the vascular endothelial growth factor (VEGF) inhibitor bevacizumab (AVASTIN®), may reduce the rate of glycolysis in tumors as a mechanism to slow tumor growth. However, tumor metabolism may then shift to mitochondrial metabolism for energy production to support continued tumor proliferation. In such cases of tumor plasticity in the presence of treatment with anti-angiogenics, contemporaneously targeting the alternative metabolic source by inhibiting ATP production with the mitochondrial drug inhibitor ME-344, may open an important therapeutic opportunity.

In a multicenter, investigator-initiated, randomized, open-label, window of opportunity clinical study, ME-344 (3 doses) plus bevacizumab (1 dose) was evaluated in 42 women with early HER2-negative breast cancer. Study results demonstrated significant biological antitumor activity in HER2-negative breast cancer patients as measured by reductions in the proliferative biomarker Ki-67 compared to placebo. The combination appeared to be generally well tolerated. The data from this study were consistent with preclinical data suggesting that ME-344 can reverse resistance to anti-angiogenic therapy and provided validation for continued evaluation of the combination of ME-344 with bevacizumab and other VEGF inhibitors.

An earlier Phase 1 clinical study evaluating ME-344 as a single-agent in patients with refractory solid tumors also demonstrated anti-tumor activity, further validating the potential of mitochondrial inhibition as a promising therapeutic modality.

About Colorectal Cancer

Colorectal cancers generally start as growths, called polyps, on the inner lining of the colon or rectum. If cancer forms in a polyp, it can grow into the wall of the colon or rectum over time, and then grow into blood vessels or lymph vessels that can allow the cancer to spread across the body. Metastatic colorectal cancer is a colorectal cancer that has already spread to other parts of the body.

Excluding skin cancers, colorectal cancers are the third most common cancer diagnosed in both men and women in the United States. It is estimated that approximately 150,000 patients will be diagnosed with colorectal cancers in the United States in 2023. Colorectal cancer is the second most common cause of cancer deaths in the U.S., with approximately 52,550 deaths expected during 2023.*

Treatment of colorectal cancer may include a combination of chemotherapy, targeted therapy, immunotherapy, surgery, and radiation therapy, which can be used to slow the spread of the disease and shrink a cancerous tumor.**

*American Cancer Society, Cancer.org (accessed July 26, 2023); **American Society of Clinical Oncology, Cancer.Net (accessed July 26, 2023).

About MEI Pharma

MEI Pharma, Inc. (Nasdaq: MEIP) is a pharmaceutical company focused on developing potential new therapies for cancer. MEI Pharma’s portfolio of drug candidates includes clinical stage candidates with differentiated mechanisms of action intended to address unmet medical needs and deliver improved benefit to patients in combination with other therapeutic options. For more information, please visit www.meipharma.com. Follow us on Twitter @MEI_Pharma and on LinkedIn.

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