On October 31, 2017 DelMar Pharmaceuticals, Inc. (Nasdaq: DMPI) ("DelMar" and "the Company"), a biopharmaceutical company focused on the development of new cancer therapies, reported the presentation of new data at the AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) which was held October 26 -30, 2017 at the Pennsylvania Convention Center in Philadelphia (Press release, DelMar Pharmaceuticals, OCT 31, 2017, View Source [SID1234521333]).
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
DelMar presented a poster entitled "DNA Damaging Agent Dianhydrogalactitol (VAL-083) Targets Homologous Repair (HR) Pathway and Suggests Combination Therapy with topoisomerase inhibitors and PARP inhibitors." A copy of this presentation can be viewed on the Company’s website. The poster summarizes recent research conducted by DelMar in collaboration with the University of Texas MD Anderson Cancer Center and the Vancouver Prostate Center. In these studies, VAL-083 was shown to rapidly introduce irreversible DNA interstrand crosslinks leading to persistent DNA double-strand breaks and cancer cell death. Treatment with VAL-083 induced S/G2 phase cell cycle arrest in all cancer cells tested, including ovarian, prostate, lung and glioma cells.
These results suggest the potential for synergy with treatments that depend on a cancer cell to be in the S-phase for activity. Such agents include topoisomerase inhibitors, commonly used in the treatment of brain cancer and other solid tumors, and PARP inhibitors, commonly used in the treatment of ovarian cancer. In combination studies, VAL-083 combined with either topoisomerase inhibitors or PARP inhibitors demonstrated synergy or super-additivity against a range of cancer cells. Topoisomerase inhibitors tested in combination with VAL-083 included etoposide and camptothecin. PARP inhibitors tested in combination with VAL-083 included olaparib, talazoparib and veliparib.
"We have previously demonstrated that VAL-083 maintains activity against cancer cells resistant to the most commonly used chemotherapies," stated Dr. Dennis Brown, DelMar’s Chief Scientific Officer. "The data presented here expand the opportunity to leverage VAL-083’s unique mechanism in combination with agents such as PARP inhibitors and topoisomerase inhibitors that are widely used the treatment of multiple cancers."
"Resistance to treatment can occur when cancer cells, or even a small group of cancer cells within a tumor, contain molecular alterations rendering them insensitive to a particular drug," continued Dr. Brown. "In other cases, cancer cells may adapt to the drug while it is being administered, acquiring molecular changes that allow them to escape its effects. We are enthusiastic about our results to date with VAL-083 as a single agent, but these data suggest the potential to further improve patient outcomes by combining VAL-083 with other anti-cancer agents that work by a different molecular mechanism. PARP inhibitors have recently gained significant interest in the treatment of ovarian cancer and are now being explored in multiple cancers. Topoisomerase inhibitors have been established as important components in the treatment of lung, ovarian, prostate and central nervous system tumors, but their utility can be limited by side effects. A synergistic combination with VAL-083 offers the potential to improve outcomes while minimizing toxic side-effects. We look forward to exploring potential combination therapy regimens especially through possible collaborations with companies currently marketing these agents."
About VAL-083
VAL-083 (dianhydrogalactitol) is a "first-in-class", DNA-targeting agent that introduces interstrand DNA cross-links at the N7-position of guanine leading to DNA double-strand breaks and cancer cell death. VAL-083 has demonstrated clinical activity against a range of cancers including GBM and ovarian cancer in historical clinical trials sponsored by the U.S. National Cancer Institutes.
VAL-083 has been granted an orphan drug designation by the U.S. FDA Office of Orphan Products for the treatment of glioma, medulloblastoma and ovarian cancer, and in Europe for the treatment of malignant gliomas.
DelMar has demonstrated that VAL-083’s anti-tumor activity is unaffected by common mechanisms of chemoresistance in vitro. Further details regarding these studies can be found at View Source