NOXXON Pharma N.V. announced positive results from the second cohort in its Phase 1/2 study of NOX-A12 in combination with radiotherapy in patients with brain cancer (Glioblastoma Multiforme). Data show that NOX-A12 at 400mg/week continues to be safe and well tolerated with apparent signals of reduction of tumor size. The study investigates three dose regimens of NOX-A12 (200, 400 and 600 mg/week), each combined with external-beam radiotherapy in newly diagnosed brain cancer patients. The six patients in the first two cohorts (3 patients receiving 200 mg/week and 3 patients receiving 400 mg/week) have now completed NOX-A12 therapy, with over 83% of these patients showing reductions in tumor size during or after NOX-A12 treatment with maximal reductions from baseline ranging from 2% to 62%2 for patients treated at 200 mg/week (1st cohort), and 28% and 71%1,2 for two patients treated at 400 mg/week (2nd cohort). These patients tolerated combined radiotherapy and NOX-A12 therapy well without any signs of dose-limiting toxicities. Two patients, one in each of the first two cohorts, achieved objective responses with tumor reductions greater than 50%, one of which occurred after cessation of NOX-A12 therapy. In three of the six patients, smaller satellite lesions that were present before therapy around the primary tumor completely disappeared. In cohort 1 (200mg/week), two of three patients have survived past the expected average survival of 10 months. Further analysis of survival in each cohort is still pending follow-up. NOX-A12 targets CXCL12 (C-X-C Chemokine Ligand 12), a key chemokine protein that communicates between tumor cells and their environment, and is designed to 1) block repair of destroyed blood vessels and 2) break tumor protection against the immune system, enabling anti-cancer immune cells, such as killer T-cells, to enter tumor tissue and attack the cancer cells. Advanced MRI imaging techniques showed that five of six patients in the first two cohorts achieved reduced blood flow to the tumor compared with baseline3, suggesting that NOX-A12 combined with radiotherapy was able to prevent blood vessel regrowth, a key mechanism of action predicted by preclinical data. The pharmacologic effect was further supported by comparison of pre-treatment to on-therapy tumor tissue from one patient in cohort 1, revealing a disappearance of CXCL12 from the barrier cells that separate the blood from the tissue, suggesting that NOX-A12 was able to effectively suppress its target4. This tissue comparison also showed an extensive reduction in the number of actively dividing tumor cells, reaching almost zero in the on-therapy sample, and clusters of expanding cytotoxic immune cells throughout the under-treatment sample. This supports the notion that NOX-A12 can facilitate an entrance of immune cells into the tumor and an anti-tumoral immune response5, already at the lowest tested dose in the study.