NRX-4972 / Nurix Therap - LARVOL DELTA

Aurora Kinase A (AURKA) Degrader Program (GlobeNewswire) - "Nurix Therapeutics announces new preclinical data...at AACR 2026....In the H82 SCLC model, twice-daily administration of NRX-4972 resulted in 60% of mice surviving to the end of the study, whereas none of the mice treated with AURKA inhibitors alisertib or LY3295668 survived....NRX-4972 also demonstrated broader and more potent synergy than an AURKA inhibitor in an in vitro screen of combination agents across triple-negative breast cancer, SCLC, and NSCLC cell lines, further supporting its therapeutic potential."

Preclinical • Lung Neuroendocrine Carcinoma • Non Small Cell Lung Cancer • Small Cell Lung Cancer • Triple Negative Breast Cancer

NRX-4972, a selective, oral, Aurora kinase A degrader, demonstrates increased efficacy in an SCLC tumor model, and greater in vitro synergy than an AURKA inhibitor (AACR 2026) - "In contrast, none of the mice treated BID with the AURKA inhibitors alisertib or LY3295668 survived to the end of the study.To evaluate the benefit of AURKA degradation over inhibition in the combination setting, we performed an in vitro synergy screen across SCLC, NSCLC, and TNBC cancer cell lines. The highest synergy scores were found in combination with NRX-4972, and more combinations with NRX-4972 resulted in synergy than with LY3295668. These data suggest that eliminating the kinase and scaffolding functions through degradation of AURKA increases the vulnerability of cancer cells to combination therapy.Collectively, NRX-4972's superior preclinical profile highlights the potential of AURKA degraders to overcome the limitations of AURKA inhibitors and achieve meaningful therapeutic benefit."

Preclinical • Breast Cancer • Hematological Malignancies • Lung Cancer • Neuroblastoma • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • Triple Negative Breast Cancer • CDK4 • MYCN • RB1

Identification of selective, orally bioavailable aurora A degraders for treatment of pediatric and adult cancers (AACR 2025) - "Compounds with oral bioavailability and CNS exposure in mice were prioritized for further development.Our lead AURKA degrader, NRX-4972, has 58% oral bioavailability in C57BL/6 mice and moderate clearance (17.5 mL/min/kg)...Analysis of tumors isolated from treated mice revealed that AURKA degraders, but not inhibitors, rapidly induced DNA damage and apoptosis.The differentiated activity of AURKA degraders compared to enzymatic inhibitors in these preclinical studies suggests the potential for improved safety and efficacy in cancer patients. The ability of AURKA degraders to penetrate the CNS not only broadens their therapeutic potential to include pediatric brain cancers such as medulloblastoma but also offers a promising avenue for treating adult cancers with brain metastases, addressing an urgent unmet medical need."

Clinical • Brain Cancer • Breast Cancer • CNS Tumor • Hematological Malignancies • Medulloblastoma • Neuroblastoma • Oncology • Solid Tumor • AURKB • CDK4 • CRBN • MYCN • RB1

Nurix Therapeutics Presents Positive Preclinical Data at the AACR 2025 Annual Meeting from Multiple Orally Available, Brain Penetrant Degraders Against Three High Value Oncology Targets (GlobeNewswire) - "In an oral presentation titled 'Identification of selective, orally bioavailable Aurora A degraders for treatment of pediatric and adult cancers,' Nurix will highlight preclinical data from studies of NRX-4972, an orally bioavailable and highly selective brain penetrant AURKA degrader. The data demonstrate that daily oral administration of NRX-4972 resulted in downregulation of MYCN as well as induction of DNA damage, apoptosis, and G2/M arrest, the latter set of effects being more pronounced in the context of degradation rather than AURKA inhibitor, which translated into significant efficacy in a model of neuroblastoma."

Preclinical • Neuroblastoma