-Potential Biomarkers of Response to CB-839 Identified in Myeloma Cells
-Synergy of CB-839 With Pomalidomide Demonstrated in Multiple Myeloma Models
SOUTH SAN FRANCISCO, CA, USA I December 8, 2014 I Calithera Biosciences, Inc. (CALA), a clinical stage biotechnology company focused on the development of novel cancer therapeutics, today announced preclinical data for its lead anti-cancer therapeutic candidate, CB-839, at the American Society of Hematology (ASH) Annual Meeting and Exposition in San Francisco, California. CB-839 is a potent, selective, orally bioavailable glutaminase inhibitor in phase I clinical trials.
“Data presented at this week’s ASH provides us with valuable insights into cellular metabolic properties that could ultimately direct our development of CB-839 towards the patients most likely to benefit from treatment. We have identified pyruvate carboxylase expression and functional read-outs of the mTORC1 pathway as possible biomarkers in our clinical studies of CB-839. Additionally, based on the pronounced synergy we observed preclinically with CB-839 and IMiDs, we are planning to initiate a Phase 1b trial treating myeloma patients with CB-839 plus pomalidomide and dexamethasone,” said Susan Molineaux, PhD, President and Chief Executive Officer of Calithera.
Preclinical data was presented in a poster titled, “Biomarkers of Response to the Glutaminase Inhibitor CB-839 in Multiple Myeloma Cells,” on December 7, 2014 (Abstract #3429). High pyruvate carboxylase expression conferred inherent resistance to CB-839; those myeloma cells that did not express high levels of pyruvate carboxylase were sensitive to CB-839. In addition, the baseline metabolic profiles of CB-839 sensitive multiple myeloma cells were different from that of insensitive cells, suggesting that nutrient state and energy storage level in myeloma cells is an important factor in determining response to CB-839. Finally, the metabolic stress induced by CB-839 led to sustained inhibition of the nutrient senor mTORC1 in sensitive cells, with downstream effects on protein synthesis, nucleotide production and glycolysis.
Calithera also presented today at ASH the results of a study investigating the preclinical anti-tumor activity of CB-839 in combination with pomalidomide, demonstrating synergistic antiproliferative effects in IMiD-resistant cells in a poster titled, “Glutaminase Inhibitor CB-839 Synergizes with Pomalidomide in Preclinical Multiple Myeloma Models,” (Abstract #4720). The combination of CB-839 and pomalidomide produced enhanced effects on metabolic and signal transduction pathways likely contributing to the synergistic anti-proliferative activity. In addition, in a multiple myeloma xenograft model, CB-839 showed significant single agent anti-tumor efficacy and displayed enhanced anti-tumor activity when combined with pomalidomide.
In addition, two posters were presented by Calithera’s collaborators. Details for the presentations are as follows:
Anti-Myeloma Activity of a Novel Glutaminase Inhibitor CB-839
Abstract #3439
Deepika Sharma Das, Ph.D., Dana Farber Cancer Institute
Poster Session 652 Myeloma: Pathophysiology and Pre-Clinical studies, excluding Therapy: Poster II
Efficacy of Novel Glutaminase Inhibitor CB-839 in Acute Myeloid Leukemia
Abstract #3763
Polina Matre, Ph.D., MD Anderson Cancer Center
Poster Session 616 Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Poster III
About Calithera Biosciences
Calithera Biosciences is a clinical-stage company focused on discovering and developing novel small molecule drugs directed against tumor metabolism and tumor immunology. Calithera’s lead clinical candidate, CB-839, is a first-in-class inhibitor of glutaminase, a critical enzyme in tumor metabolism, and is currently being tested in patients with solid and hematological cancers. Calithera Biosciences is headquartered in South San Francisco. For more information about Calithera Biosciences, please visit www.calithera.com.
SOURCE: Calithera Biosciences
Post Views: 104
-Potential Biomarkers of Response to CB-839 Identified in Myeloma Cells
-Synergy of CB-839 With Pomalidomide Demonstrated in Multiple Myeloma Models
SOUTH SAN FRANCISCO, CA, USA I December 8, 2014 I Calithera Biosciences, Inc. (CALA), a clinical stage biotechnology company focused on the development of novel cancer therapeutics, today announced preclinical data for its lead anti-cancer therapeutic candidate, CB-839, at the American Society of Hematology (ASH) Annual Meeting and Exposition in San Francisco, California. CB-839 is a potent, selective, orally bioavailable glutaminase inhibitor in phase I clinical trials.
“Data presented at this week’s ASH provides us with valuable insights into cellular metabolic properties that could ultimately direct our development of CB-839 towards the patients most likely to benefit from treatment. We have identified pyruvate carboxylase expression and functional read-outs of the mTORC1 pathway as possible biomarkers in our clinical studies of CB-839. Additionally, based on the pronounced synergy we observed preclinically with CB-839 and IMiDs, we are planning to initiate a Phase 1b trial treating myeloma patients with CB-839 plus pomalidomide and dexamethasone,” said Susan Molineaux, PhD, President and Chief Executive Officer of Calithera.
Preclinical data was presented in a poster titled, “Biomarkers of Response to the Glutaminase Inhibitor CB-839 in Multiple Myeloma Cells,” on December 7, 2014 (Abstract #3429). High pyruvate carboxylase expression conferred inherent resistance to CB-839; those myeloma cells that did not express high levels of pyruvate carboxylase were sensitive to CB-839. In addition, the baseline metabolic profiles of CB-839 sensitive multiple myeloma cells were different from that of insensitive cells, suggesting that nutrient state and energy storage level in myeloma cells is an important factor in determining response to CB-839. Finally, the metabolic stress induced by CB-839 led to sustained inhibition of the nutrient senor mTORC1 in sensitive cells, with downstream effects on protein synthesis, nucleotide production and glycolysis.
Calithera also presented today at ASH the results of a study investigating the preclinical anti-tumor activity of CB-839 in combination with pomalidomide, demonstrating synergistic antiproliferative effects in IMiD-resistant cells in a poster titled, “Glutaminase Inhibitor CB-839 Synergizes with Pomalidomide in Preclinical Multiple Myeloma Models,” (Abstract #4720). The combination of CB-839 and pomalidomide produced enhanced effects on metabolic and signal transduction pathways likely contributing to the synergistic anti-proliferative activity. In addition, in a multiple myeloma xenograft model, CB-839 showed significant single agent anti-tumor efficacy and displayed enhanced anti-tumor activity when combined with pomalidomide.
In addition, two posters were presented by Calithera’s collaborators. Details for the presentations are as follows:
Anti-Myeloma Activity of a Novel Glutaminase Inhibitor CB-839
Abstract #3439
Deepika Sharma Das, Ph.D., Dana Farber Cancer Institute
Poster Session 652 Myeloma: Pathophysiology and Pre-Clinical studies, excluding Therapy: Poster II
Efficacy of Novel Glutaminase Inhibitor CB-839 in Acute Myeloid Leukemia
Abstract #3763
Polina Matre, Ph.D., MD Anderson Cancer Center
Poster Session 616 Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Poster III
About Calithera Biosciences
Calithera Biosciences is a clinical-stage company focused on discovering and developing novel small molecule drugs directed against tumor metabolism and tumor immunology. Calithera’s lead clinical candidate, CB-839, is a first-in-class inhibitor of glutaminase, a critical enzyme in tumor metabolism, and is currently being tested in patients with solid and hematological cancers. Calithera Biosciences is headquartered in South San Francisco. For more information about Calithera Biosciences, please visit www.calithera.com.
SOURCE: Calithera Biosciences
Post Views: 104
