DelMar Pharmaceuticals, Inc. (OTCQX: DMPI) ("DelMar" and the "Company"), a biopharmaceutical company focused on developing and commercializing proven cancer therapies in new orphan drug indications, presented additional preclinical data at the American Association of Cancer Research (AACR) Advances in Brain Cancer Research Conference on the potential for its lead product candidate VAL-083 (dianhydrogalactitol) to treat patients with temozolomide-resistant glioblastoma multiforme (GBM).
Dennis Brown, DelMar's co-Founder and Chief Scientific Officer, presented an abstract entitled, "Dianhydrogalactitol inhibits the growth of glioma stem and non-stem cultures, including temozolomide-resistant cell lines, in vitro and in vivo."
The data from the in vitro portion and the first in vivo segments of the study previously reported at the 2015 AACR annual meeting demonstrated that:
- VAL-083 may be efficacious against both stem and non-stem GBM cell cultures, including those resistant to temozolomide (TMZ);
- VAL-083 maintained anti-tumor activity independent of DNA repair enzyme 0-6-methylguanine DNA methyltransferase (MGMT) resistance mechanism;
- VAL-083 showed an additive effect when combined with radiation in all cultures tested, suggesting that VAL-083 might act as a radiosensitizer in GBM; and
- VAL-083 was effective against GBM in significantly extending survival time in intracranial xenograft GBM models in a dose dependent manner, including in GBM xenografts that are traditionally resistant to TMZ.
Data reported at the AACR Advances in Brain Cancer poster session further examined the activity of VAL-083 in in vivo models of drug-resistant GBM in comparison to TMZ. BT74 animal models bearing intracranial human GBM xenograft tumors of either MGMT-positive or TMZ-resistant origin were treated with VAL-083.
The data demonstrated that VAL-083 may be effective against GBM in extending survival time in intracranial models in a dose-dependent manner. In the first model (U251), median survival time for animals treated with 4 mg/kg VAL-083 was significantly increased to 72 days compared to 48 days for controls (p<0.0001). Median survival time for 3 mg/kg VAL-083 was 54 days. In the second in vivo model (BT74) reported yesterday, the additional data showed that VAL-083 treatment increased survival time in animals bearing intracranial BT74 tumors compared to untreated control. BT74 tumors are traditionally resistant to TMZ.
"VAL-083 has shown encouraging potential to address a significant unmet medical need in GBM patients who fail or are unlikely to respond to today's standard of care. These data continue to further support the potential benefits of VAL-083 in GBM and in our ongoing Phase 1/2 clinical study with VAL-083 as a potential treatment for refractory GBM," stated Jeffrey Bacha, DelMar's president and CEO. "In addition, VAL-083 may offer a potential alternative to the current standard of care, TMZ plus radiation, in newly diagnosed GBM patients whose tumors express high levels of the repair enzyme, O6-methylguanine methyltransferase (MGMT), which is correlated with TMZ resistance and poor patient outcomes."
The standard of care for GBM patients today is surgical resection followed by TMZ and radiation therapy. MGMT-mediated resistance has emerged as a significant unmet medical need. VAL-083 is an alkylating agent whose cytotoxic anti-cancer mechanism is believed to be via the formation of DNA crosslinks at N7 position of guanine. Because these N7 adducts appear not to be subject to MGMT-mediated repair, VAL-83 may be an effective chemotherapeutic in the treatment of TMZ-resistant GBM. VAL-083 has been demonstrated to cross the blood brain barrier and accumulate in brain tumor tissue. Previous studies show that TMZ activity is similar in cancer stem cells (CSC) and their paired non-CSC from primary GBM tissues independent of their MGMT expression.
The poster presentation for this study may be found on the DelMar Pharmaceuticals website under the Scientific Publications & Presentations section.
DelMar Pharmaceuticals, Inc.