Nurix Therapeutics presented new preclinical data at the American Association for Cancer Research (AACR) Annual Meeting in Brisbane, California, highlighting three oncology programs: the pan‑mutant BRAF degrader NRX‑0305, the CBL‑B inhibitor NX‑1607, and the Aurora Kinase A degrader NRX‑4972.
NRX‑0305 is an orally bioavailable, CNS‑penetrant degrader that showed dose‑proportional pharmacokinetics and robust degradation of mutant BRAF in intracranial melanoma and glioma models. In a BRAF‑resistant melanoma brain metastasis patient‑derived xenograft, the compound extended survival by 142%, compared with a 12% increase for the approved BRAF inhibitor dabrafenib. The data also demonstrated activity across 14 patient‑derived xenograft models spanning Class 1, 2, and 3 BRAF mutations, and showed single‑agent and combination efficacy with MEK inhibitors or anti‑EGFR therapy.
NX‑1607 is the first‑in‑class intramolecular glue inhibitor of the E3 ligase CBL‑B. It enhances T‑cell activation, increasing IL‑2 and IFN‑γ secretion in response to TCR stimulation. In syngeneic tumor models—including colorectal, triple‑negative breast cancer, and B‑cell lymphoma—NX‑1607 produced single‑agent anti‑tumor activity and synergized with anti‑PD‑1 therapy to significantly improve survival. Early clinical data revealed dose‑dependent pharmacokinetics and target engagement in CD8 T cells.
NRX‑4972 is a selective, oral Aurora Kinase A degrader that penetrates the central nervous system and shows superior antitumor activity in a small cell lung cancer (SCLC) model. Twice‑daily dosing resulted in 60% of mice surviving to the study end, whereas none survived with the AURKA inhibitors alisertib or LY3295668. Mechanistically, degradation of AURKA down‑regulated MYC and induced DNA damage, apoptosis, and G2/M arrest, and the degrader demonstrated greater synergy than an inhibitor in triple‑negative breast cancer, SCLC, and NSCLC cell lines.
Arthur T. Sands, M.D., Ph.D., president and chief executive officer, said, "These data, together with our participation in the AACR Advances session, highlight the growing clinical and scientific validation of targeted protein degradation as a new therapeutic modality. Across multiple programs, we are seeing consistent evidence that these therapies can drive deeper and more durable biological responses, supporting their potential to deliver meaningful benefit for patients."
The robust preclinical data support the advancement of these candidates toward clinical development and strengthen Nurix’s position in the targeted protein degradation space, addressing unmet needs in oncology and reinforcing investor confidence in the company’s pipeline.
The content on EveryTicker is for informational purposes only and should not be construed as financial or investment advice. We are not financial advisors. Consult with a qualified professional before making any investment decisions. Any actions you take based on information from this site are solely at your own risk.