MEI Pharma, Inc. (NASDAQ:MEIP) is a clinical-stage pharmaceutical company committed to developing novel and differentiated cancer therapies. The company's pipeline includes two promising drug candidates - voruciclib, an oral cyclin-dependent kinase 9 (CDK9) inhibitor, and ME-344, an intravenous small molecule inhibitor of mitochondrial oxidative phosphorylation (OXPHOS).
Business Overview
MEI Pharma builds its pipeline by acquiring promising cancer agents and creating value through clinical development, strategic partnerships, and out-licensing or commercialization. The company's approach to oncology drug development is to evaluate its drug candidates in combinations with standard-of-care therapies to overcome known resistance mechanisms and address clear medical needs to provide improved patient benefit.
Voruciclib: Targeting MCL-1 and MYC
Voruciclib is a selective oral CDK9 inhibitor that regulates the transcription of MCL-1 and MYC, two important targets in cancer. MCL-1 is associated with poor prognosis in acute myeloid leukemia (AML) and B-cell malignancies, and its upregulation is a known resistance mechanism to the BCL-2 inhibitor venetoclax. MYC is overexpressed in various cancers and is linked to poor prognosis.
MEI is currently evaluating voruciclib as a single agent and in combination with venetoclax in a Phase 1 trial in patients with relapsed/refractory AML and B-cell malignancies. The monotherapy dose escalation component has been completed, with 40 patients enrolled. Voruciclib at doses up to 200 mg administered on a 14 days on, 14 days off schedule was well-tolerated, with evidence of anti-tumor activity, including one patient with AML achieving a morphologic leukemia-free state and five of 10 patients with AML at the 200 mg dose having stable disease.
The company is now enrolling patients in the combination with venetoclax stage of the study. Initial results from this stage have shown that voruciclib at doses of 100 mg or more in combination with venetoclax was well-tolerated, and three patients achieved responses, including two complete responses with incomplete hematologic recovery and one morphologic leukemia-free state, in each case having received venetoclax in an earlier line of treatment. An additional 14 patients had stable disease lasting more than 90 days. Biomarker analyses have demonstrated the anticipated decreases in MCL-1, supporting the hypothesis that voruciclib can address the upregulation of MCL-1 associated with venetoclax resistance.
ME-344: Targeting Tumor Metabolism
ME-344 is a novel drug candidate that inhibits mitochondrial OXPHOS, a fundamental metabolic pathway involved in the production of adenosine triphosphate (ATP) in the mitochondria. By disrupting the production of ATP, ME-344 has been shown to induce cancer cell death in nonclinical models.
MEI is pursuing a novel approach to cancer therapy with a combination of ME-344 and bevacizumab (Avastin®), a VEGF inhibitor. When bevacizumab is administered, it blocks the glycolytic energy pathway, leading to a reduction in ATP production through glycolysis. By combining ME-344 to block the mitochondrial energy pathway, the company believes this may induce synthetic lethality and improve anti-tumor control.
A previous investigator-initiated, randomized, controlled clinical trial in 42 patients with HER2-negative breast cancer demonstrated significant biologic activity in the ME-344 treatment group, with mean absolute and relative decreases in the proliferation marker Ki67 compared to the bevacizumab monotherapy group.
Building on these results, MEI is now conducting a Phase 1b study evaluating ME-344 in combination with bevacizumab in patients with relapsed metastatic colorectal cancer (mCRC) after failure of standard therapies. In the first cohort of 23 patients, the combination was generally well-tolerated, and 5 of 20 evaluable patients (25%) completed 16 weeks of therapy without evidence of disease progression, exceeding the pre-determined threshold to proceed to the second cohort. The median progression-free survival was 1.9 months, and the median overall survival was 6.7 months.
Financials
For the fiscal year ended June 30, 2023, MEI reported annual revenue of $48.8 million and a net loss of $31.8 million. The company's annual operating cash flow and free cash flow were -$52.5 million and -$52.5 million, respectively.
Liquidity
As of March 31, 2024, MEI had $56.6 million in cash, cash equivalents, and short-term investments, which the company believes will be sufficient to fund operations for at least the next 12 months and through the reporting of clinical data readouts from the ongoing and planned voruciclib and ME-344 Phase 1 and Phase 1b clinical programs.
Risks and Challenges
MEI's pipeline is promising and presents substantial opportunity for delivering novel therapeutics for patients and value creation for shareholders. Both voruciclib and ME-344 have the potential, in combination with current standards of care therapies, to overcome known resistance mechanisms and improve patient outcomes.
Outlook
The company expects to report data from the voruciclib program in early 2024 and from the ME-344 program in the first half of 2024. These data readouts will be crucial in informing the next steps for each program. While the company's current cash position provides a runway of at least 12 months, additional capital may be required in the future to support the continued development and potential commercialization of its drug candidates.
Conclusion
Overall, MEI Pharma's focus on novel mechanisms of action and combination approaches to address unmet needs in oncology makes it an interesting investment opportunity for those willing to take on the risks inherent in a clinical-stage biopharmaceutical company. The upcoming data readouts will be pivotal in determining the future direction and value potential of the company's pipeline.