ARCHAMPS, France—Taking one step closer toward one day finding a way to slow cancer’s deadly wrath, French biopharmaceutical Genkyotex has completed a study indicating that data in multiple preclinical models shows that GKT831, the company's NOX1 and NOX4 inhibitor, efficiently targeted cancer-associated fibroblasts (CAFs) and delayed tumor growth. The results were published August 3, 2017, in the online version of the Journal of the National Cancer Institute.
The study not only brought hope to cancer patients, but to oncologists looking for more effective treatment options. The study also earned Prof. Gareth Thomas of the University of Southampton in the United Kingdom a Small Molecule Drug Discovery grant from Cancer Research UK to develop clinical strategy for GKT831 in oncology. The title of the two-year grant is “Targeting cancer-associated fibroblasts via NOX1/4 inhibition: adjunctive therapy for oral cancer treatment.” The grant amount is undisclosed.
“Fibroblasts (CAFs) have been shown to protect tumor cells from chemotherapy and are also involved in tumor immune evasion,” senior author Thomas says. “In this grant, we will be examining whether we can improve response rates to standard-of-care chemotherapy (cisplatin, 5FU) and immunotherapy (anti-PD1), and anti-tumor vaccination in murine syngeneic oral cancer models by combining these therapies with GK831 to simultaneously target the CAF population.”
Elias Papatheodorou, CEO of Genkyotex, tells DDNews, “The announcement of the third of August confirms the role of NOX enzymes in the activation of myofibroblasts (including cancer-associated fibroblasts) and the potential of NOX inhibitors as targeted therapies in fibrosis and in multiple cancers.”
“We evaluate that fibrosis is involved in 45 percent of all deaths in the developed world,” Papatheodorou says. “It’s a severe disease reaching multiple organs including liver, kidney and lung, and has been shown through many preclinical models with GKT831 that NOX1 and NOX 4 are involved in multiple clinically validated fibrogenic pathways.”
This model “further demonstrates the importance of NOX enzymes in fibrogenesis and the importance of NOX4 in the activation of cancer-associated fibroblasts (CAFs),” he adds.
According to Papatheodorou, Genkyotex “is progressing in the development of its main molecule GKT831 in fibrosis diseases first in the liver with a Phase 2 clinical trial in PBC, for which we announced on June 27 the initiation of patient enrollment. We also announced an investigator-initiated Phase 2 clinical trial to evaluate GKT831 in patients with type 1 diabetes and kidney disease. This will be a second fibrotic indication explored in the clinic with GKT831.”
Genkyotex’s Phase 2 clinical trial of GKT831, its NOX1 and NOX4 enzymes inhibitor, is in primary biliary cholangitis (PBC), a progressive fibrotic liver disease. Dosing of the first patient is expected shortly, with interim top-line results from the Phase 2 clinical trial anticipated in the first half of 2018, and full results expected in the second half of 2018, Papatheodorou says.
“This compound will also enter into a Phase 2 clinical trial to evaluate its efficacy and safety in patients with type 1 diabetes and kidney disease (diabetic kidney disease),” he notes. “This trial, fully funded by the Juvenile Diabetes Research Foundation (JDRF), Australia and the Baker Institute, is expected to begin patient enrollment during the second half of 2017.”
Genkyotex is also “actively working on preclinical models to show the importance of NOX enzymes in CNS [central nervous system] and hearing loss,” he adds. “We are now focused on assessing the impact of GKT831 on improving the response of certain common cancers to immunotherapy and chemotherapy.”
Dr. Philippe Wiesel, executive vice president and chief medical officer of Genkyotex, stated in a news release, “We are very impressed by these results which suggest that NOX4 inhibition with GKT831 can effectively target the tumor stroma. Importantly, this may have broad applicability across many common cancer types.”
“We are proud of our accomplishments over the first half of 2017. The clinical development of GKT831 is broader than initially announced at the beginning of the year. We are confident in both the medical potential of our therapies and in our ability to potentially bring them closer to patients suffering from fibrotic diseases,” Papatheodorou concludes.