Calithera Biosciences Highlights Results From Six Preclinical Abstracts

Calithera Biosciences, Inc.

a clinical-stage pharmaceutical company focused on discovering and developing novel small molecule drugs directed against tumor metabolism and tumor immunology targets for the treatment of cancer, today will announce preclinical data for its lead anti-cancer therapeutic candidate, CB-839, Calithera's novel, orally bioavailable glutaminase inhibitor, at the American Association for Cancer Research, taking place April 18-22, 2015 in Philadelphia, Pennsylvania. CB-839 is a potent, selective, orally bioavailable glutaminase inhibitor in phase I clinical trials. "We have identified KRAS and EGFR mutation status as potential biomarkers correlated to enhanced sensitivity of CB-839, which could ultimately direct our development of CB-839 in non-small cell lung cancer. In addition, based on our synergy studies, CB-839 in combination with signal transduction inhibition may offer a novel therapeutic strategy for the treatment of non-small cell lung cancer and renal cell carcinoma," said Susan Molineaux, PhD, President and Chief Executive Officer of Calithera. Preclinical data will be presented by Lindsey Boroughs from the laboratory of Ralph Debaradinis at the University of Texas Southwestern in an oral session titled, "Evaluation of the glutaminase inhibitor CB-839 in non-small cell lung cancer," on April 21, 2015 (Abstract #4710). In this session, data will be presented demonstrating that lung cancer cell lines carrying EGFR or KRAS mutations have enhanced sensitivity to CB-839. Additional preclinical data from Calithera will be presented by Frank Parlati, Senior Director of Biology, in an oral session titled "CB-839, a selective glutaminase inhibitor, synergizes with signal transduction pathway inhibitors to enhance anti-tumor activity," (Abstract #4711). Signaling through mTOR is down regulated by CB-839, demonstrating a relationship between signal transduction pathways and cancer metabolism. CB-839 also synergizes with the mTOR inhibitor everolimus in renal clear cell carcinoma lines. In addition, CB-839 has synergistic activity with the MEK inhibitor selumetinib in KRAS mutant lung cancer cell lines both in vitro and in vivo, and with the EGFR inhibitor erlotinib in EGFR mutant lung cancer cell lines as well as in erlotinib-resistant EGFR mutant animal models lacking the T790M mutation. CB-839 was also the subject of a poster presented by Calithera's collaborator Arimichi Okazaki from the Laboratory of Othon Iliopoulos at the Massachusetts General Hospital titled, "Glutaminase inhibitors suppress pyrimidine synthesis and promote DNA replication stress in Von Hippel-Lindau (VHL) deficient human renal cells (Abstract #1123)." The data demonstrate that CB-839 induces double stranded breaks in VHL deficient renal cell carcinoma cells and that PARP (Poly ADP-ribose polymerase) inhibitors synergize with CB-839 in these cells. Three additional presentations at the meeting include: Targeting glucose and glutamine regulated BCL2 family members for multiple myeloma therapy Abstract #972 Presenter: Richa Bajpai, Winship Cancer Institute, Emory University Sunday, April 19, 2015 CB839, an orally bioavailable glutaminase inhibitor, shows potent antitumor activity in vitro against models of soft tissue sarcoma and chondrosarcoma Abstract #4450 Presenter: Tahir Sheikh, Laboratory of Gary Schwartz, Columbia University Tuesday, April 21, 2015 A new anticancer strategy based on inhibiting mitochondrial proline dehydrogenase (PRODH) and exploiting synthetic lethal interactions with p53 restoration and/or glutaminase (GLS1) inhibition Abstract #5402 Presenter: Gary Scott, Laboratory of Christopher Benz, Buck Institute Wednesday, April 22, 2015 The meeting abstracts can be viewed online through the AACR website at www.aacr.org.