NRX-0305

NRX-0305 is a potent, selective, and orally bioavailable pan-mutant BRAF degrader developed by Nurix Therapeutics for oncology indications. It is designed to degrade all three classes of oncogenic mutant BRAF proteins (Class 1, 2, and 3) while sparing wildtype BRAF in healthy cells. The drug demonstrates broad anti-tumor efficacy in preclinical models of melanoma, non-small cell lung cancer (NSCLC), colorectal cancer (CRC), and other solid tumors harboring BRAF mutations—including those resistant to existing therapies. Notably, NRX-0305 is brain penetrant and shows activity against CNS disease models as well as synergy with MEK inhibitors such as trametinib. Its mechanism involves targeted protein degradation rather than simple inhibition, aiming to overcome resistance seen with current BRAF inhibitors[1][2][4][5][8][9].