Calithera Biosciences Presents Pharmacodynamic Data on CB-839 at the 2014 American Association for Cancer Research Annual Meeting
“The pharmacodynamic assay for CB-839 presented at the AACR Annual Meeting is already being employed in our clinical development of CB-839,” said
Although CB-839 is a reversible inhibitor of glutaminase, the Calithera team identified assay conditions that stabilized the enzyme-inhibitor complex and enabled direct measurement of inhibition in tissues. Using this assay, dose escalation studies in tumor-bearing mice established that maintaining a 300 nM plasma concentration of CB-839 was sufficient to maximally inhibit glutaminase in tumors. Ex vivo treatment of human whole blood with CB-839 gave similar results, showing that a concentration of 300 nM CB-839 was sufficient to achieve > 90% inhibition of glutaminase in platelets. Preliminary data from patients receiving a low dose of CB-839 in one of Calithera’s ongoing Phase 1 dose-escalation trials verified this finding. A 100 mg dose of CB-839, which resulted in peak plasma levels of drug at or above 300 nM, generated > 80% inhibition of glutaminase in platelets four hours after dosing.
These data were presented during the Cancer Metabolism: New Pathways and ProgressToward Therapy minisymposium in a talk titled: “Novel pharmacodynamic assays to measure glutaminase inhibition following oral administration of CB-839″ (Abstract #966).
Calithera researchers also shared preclinical data in a poster detailing CB-839′s antiproliferative activity in a range of solid and hematologic tumor types. Glutaminase has potent in vitro anti-tumor activity across many tumor types, including triple-negative breast cancer, non-small cell lung cancer, mesothelioma, multiple myeloma and other B-cell malignancies. A strong correlation was seen across the tumor cell line panel between the response to CB-839 and the dependence on glutamine for growth and survival. These results were presented in a poster titled, “CB-839, a novel, potent and selective glutaminase inhibitor, has broad antiproliferative activity in cell lines derived from both solid tumors and hematological malignancies” (Abstract # 1416).
About Calithera Biosciences
Calithera Biosciences, Inc. is a clinical-stage company focused on the discovery, development and commercialization of first-in-class small molecule oncology therapeutics. The company is building a pipeline of targeted anti-cancer compounds that inhibit pathways critical to tumor growth and survival. Calithera’s lead clinical candidate, CB-839, blocks glutaminase, an enzyme critical to tumor metabolism, and is currently being tested in patients with advanced solid and hematological cancers. Calithera Biosciences is headquartered in
SOURCE Calithera Biosciences