Nurix Therapeutics presented new preclinical data across its oncology pipeline at the AACR Annual Meeting showcasing mechanistic validation of targeted protein degradation programs against pan-mutant BRAF, CBL-B and Aurora kinase A targets, emphasizing the approach’s potential to overcome inhibitor limitations and broaden therapeutic reach.

NRX-0305 is an orally bioavailable, CNS-penetrant pan-mutant BRAF degrader that demonstrated dose-proportional pharmacokinetics and robust mutant BRAF degradation, delivering a 142% survival increase in a BRAF inhibitor–resistant melanoma brain metastasis PDX model versus ~12% with dabrafenib and exhibiting efficacy across 14 mutant BRAF PDX models with MEKi or anti-EGFR combinations.

NX-1607, a first-in-class CBL-B intramolecular glue inhibitor with sub-nanomolar binding affinity, stabilized the inactive CBL-B conformation to enhance T cell activation as shown by increased IL-2 and IFN-γ secretion, produced single-agent tumor suppression in colorectal, breast and lymphoma models, synergized with anti-PD-1 therapy and demonstrated dose-dependent PK/PD target engagement in early clinical studies.

NRX-4972, a selective oral Aurora kinase A degrader with CNS penetration, achieved superior antitumor activity compared to AURKA inhibitors in SCLC models, with a twice-daily regimen yielding 60% survival versus 0% for inhibitors, driven by MYC downregulation and enhanced DNA damage, apoptosis and G2/M arrest, and showed broader in vitro combination synergies.