EPISENSITIZATION AND RRx-001
EpicentRx’s lead compound is called RRx-001, a structurally unique pharmacophore that inhibits multiple epi-enzymes and independently affects the apoptosis pathway and reactive oxygen and nitrogen species (RONS) production. RRx-001 is not cross-resistant with approved therapies and selectively targets and resensitizes hypoxic tumor cells to immunotherapy, chemotherapy and radiotherapy.
RRx-001 has successfully completed a Phase 1 “all comers” dose escalation study in 25 patients with advanced, refractory cancer in which safety and activity were demonstrated in all six cohorts tested and in a variety of tumor types. Results from the Phase I trial are available in Lancet Oncology, August 2015. To read the press release visit this link.
The success of the Phase 1 study was the springboard for further clinical development in multi-site biomarker-driven Phase 2 trials, as single agent and in combination with other anti-cancer drugs and with radiotherapy.
Preclinical data has demonstrated a synergistic combination of RRx-001 and radiotherapy that EpicentRx plans to explore fully in the clinical setting.
The ROS-mediated epigenetic mechanism of action elicited by RRx-001 lead to a suite of antitumor responses including immune upregulation, reinduction of p53, anti-energetic glycolytic inhibition, and G6PD inhibition ultimately culminating in ‘episensitization’ which experimentally enhances drug combinatorial effects and resensitizes chemoresistant and immunoresistant tumors to previously failed therapies.
Since RRx-001 increases the responsiveness of tumor cells to chemotherapy at least in part through reactions, which locally increase oxidative and nitrosative stress, it literally represents a radical approach to cancer treatment.
During 2014-2015 EpicentRx has launched Phase 2 trials in brain, colorectal, non-small cell lung, small cell lung and cholangiocarcinoma both alone and in combination.