On April 10, 2021 MEI Pharma, Inc. (NASDAQ: MEIP), a late-stage pharmaceutical company focused on advancing new therapies for cancer, reported preclinical data demonstrating that voruciclib, an orally administered cyclin-dependent kinase (CDK) inhibitor that is potent against CDK9, has single agent activity against multiple KRAS mutant cancer cell lines and synergistically inhibits growth of KRAS mutant cancers in combination with KRAS inhibitors (Press release, MEI Pharma, APR 10, 2021, View Source [SID1234577830]). The research is featured as an E-Poster Session presentation titled, "Voruciclib, a CDK9 inhibitor, downregulates MYC and inhibits proliferation of KRAS mutant cancers in preclinical models" at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2021. Voruciclib is currently in a Phase 1b clinical trial as a monotherapy in patients with relapsed and/or refractory B-cell malignancies and acute myeloid leukemia (AML).
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To view the poster and a multimedia announcement with additional media and investor resources click here.
"Collectively, the data reported today offer the opportunity to expand our current development activities with voruciclib and support its potential as a therapeutic option for KRAS mutated cancers in combination with direct inhibitors of KRAS," said Daniel P. Gold, Ph.D., president and chief executive officer of MEI Pharma. "Beyond these data, we have ongoing efforts to explore other potential synergistic combinations in various KRAS mutated cancers as we evaluate opportunities to confirm these findings in a clinical setting."
KRAS mutated cancers are frequently associated with overexpression of MYC, a transcription factor regulating cell proliferation and growth. CDK9 is a known regulator of MYC transcription and a modulator of MYC protein phosphorylation. The data reported today in preclinical models demonstrates that voruciclib:
Results in a rapid decrease in the phosphorylation of proteins that promote MYC transcription
Rapidly decreases phosphorylation of MYC protein on Ser62, a site implicated in stabilizing MYC in KRAS mutant cancers
Possesses single agent activity against multiple KRAS mutant cancer cell lines both in vitro and in vivo
Synergistically inhibits KRAS G12C mutant cancer cell lines in combination with KRAS G12C inhibitors, both in vitro and in vivo
The full video presentation is available on our website here: View Source
About Voruciclib
Voruciclib is an orally administered CDK inhibitor differentiated by its potent in vitro inhibition of CDK9 in addition to CDK6, 4 and 1. CDK9 has important functions in cell cycle regulation, including the modulation of two therapeutic targets in cancer:
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 ("BCL2") inhibitor venetoclax (marketed as Venclexta).
CDK9 is a transcriptional regulator of the MYC proto-oncogene protein ("MYC") which regulates cell proliferation and growth. Upregulation of MYC is implicated in many human cancers and is frequently associated with poor prognosis and unfavorable patient survival. CDK9, in addition to being a transcription factor for MYC, also decreases phosphorylation of MYC protein that is implicated in stabilizing MYC in KRAS mutant cancers. Targeting MYC directly has historically been difficult, but CDK9 is a promising approach to target this oncogene.
Voruciclib is currently being evaluated in a Phase 1b trial evaluating dose and schedule in patients with acute myeloid leukemia ("AML") and B-cell malignancies. Applications in solid tumors are also being explored, particularly in KRAS mutated cancers.
Investor and Analyst Video Webcast
MEI will host an investor and analyst video webcast event on Tuesday, April 13, 2021 at 8:00 AM Eastern Time reviewing data from the E-Poster Session presentation at AACR (Free AACR Whitepaper), in which MEI reported data demonstrating voruciclib downregulates MYC and synergizes with KRAS inhibitors to inhibit KRAS mutant cancers in preclinical models. The event will also include additional voruciclib data as well as an overview and update of MEI’s business.
You can access the live video webcast under the investor relations section of MEI’s website on the "Events and Presentation" page at: www.meipharma.com. A replay of the video webcast will be archived for at least 30 days after the conclusion of the live event.