On December 1, 2018 MEI Pharma, Inc. (NASDAQ: MEIP), a late-stage pharmaceutical company focused on advancing new therapies for cancer, reported preclinical data presented at the 2018 American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting demonstrating that voruciclib, MEI’s orally available CDK9 inhibitor, synergistically induced apoptosis at clinically relevant concentrations when combined with venetoclax (marketed as Venclexta) in human derived acute myeloid leukemia (AML) cells lines and patient samples (Press release, MEI Pharma, DEC 1, 2018, View Source [SID1234531766]). Voruciclib is currently being evaluated in a Phase 1b dose ranging study in patients with B-cell malignancies.
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The data presented today demonstrate the synergistic induction of apoptosis of voruciclib when combined with venetoclax via the transient downregulation of MCL1 in multiple AML cell lines and patient samples. Inhibition of CDK9 blocks the production of MCL1, which is an established resistance mechanism to the BCL-2 inhibitor venetoclax.
"This study evaluating the synergistic activity of voruciclib in AML cells builds on existing preclinical data demonstrating similar activity in other B-cell malignancies, including diffuse large B-cell lymphoma and chronic lymphocytic leukemia, and reinforces the significant clinical utility voruciclib may hold when combined with inhibitors of BCL-2 in B-cell disease," said Daniel P. Gold, Ph.D., president and chief executive officer of MEI Pharma. "As we progress in our ongoing Phase 1 study, we look forward to selecting the voruciclib clinical dose to evaluate in combination with venetoclax to clinically assess synergies and the opportunity for combination treatments across multiple indications."
The voruciclib ASH (Free ASH Whitepaper) 2018 poster can be accessed on the MEI Pharma website.
About Voruciclib
The CDK family of proteins are important cell cycle regulators. CDK9 is a transcriptional regulator of the myeloid leukemia cell differentiation protein ("MCL1"), a member of the family of anti-apoptotic proteins which, when elevated, may prevent the cell from undergoing cell death. Inhibition of CDK9 blocks the production of MCL1, which is an established resistance mechanism to the B-cell lymphoma ("BCL-2") inhibitor venetoclax.
CDK9 is also a transcriptional regulator of MYC, a transcription factor regulating cell proliferation and growth which contributes to many human cancers and is frequently associated with poor prognosis and unfavorable patient survival. Targeting MYC directly has historically been difficult, but CDK9 is a transcriptional regulator of MYC and is a promising approach to target this oncogene.
In August 2018 MEI dosed the first patient in a dose ranging Phase 1b clinical trial of voruciclib as a single agent in patients with relapsed and/or refractory B-cell malignancies after failure of prior standard therapies to determine the safety, preliminary efficacy and maximum tolerated dose. We also plan to evaluate voruciclib in combination with venetoclax to assess synergies and the opportunity for combination treatments across multiple indications.