Nurix Therapeutics reports ‘positive’ data from Phase 1 trial of NX-2127

Nurix Therapeutics presented additional positive clinical data from its Phase 1 clinical trial of NX-2127 in two oral sessions by Anthony Mato, M.D., MSCE, former director of the Chronic Lymphocytic Program at Memorial Sloan Kettering Cancer Center, and Omar Abdel-Wahab, M.D., Chair of Sloan Kettering Institute Molecular Pharmacology Program at Memorial Sloan Kettering Cancer Center. NX-2127 is a once daily, oral, investigational new drug that combines BTK degradation with immunomodulatory activity. The podium presentations took place at the 64th American Society of Hematology Annual Meeting and Exposition which is being held in New Orleans, Louisiana. "These early Phase 1 data demonstrate that NX-2127 effectively degrades BTK resulting in clinically meaningful responses independent of prior treatments or BTK mutational status and offering a potential new treatment modality for patients who have otherwise exhausted other approved and emerging treatment options," said Robert J. Brown, M.D., Nurix’s executive vice president of clinical development. The data presented by Dr. Mato demonstrate that treatment with NX-2127 results in sustained BTK degradation and clinically meaningful responses in heavily pretreated patients with relapsed/refractory CLL independent of prior treatments or BTK mutational status. These presentations included preliminary data from 36 adults with relapsed/refractory B-cell malignancies enrolled in the Phase 1a/b study, including 23 patients with CLL who had undergone and failed a median of five prior therapies including a BTK inhibitor. Approximately 78% of this group had previously received both BTK and BCL2 inhibitors and 35% had been treated with the non-covalent BTK inhibitor pirtobrutinib. Of the CLL patients, 48% had one or more identified BTK resistance mutations prior to treatment with NX-2127. Following treatment with NX-2127 in this heavily pretreated CLL population, sustained BTK degradation and decreased B cell activation were observed regardless of prior treatment and baseline BTK mutation status with an overall response rate of 33%. As of September 21, 2022, the data cut-off date, the median follow up was 5.6 months, and 14 of 23 patients remained on treatment. Importantly, the safety profile of NX-2127 was consistent with prior results from the Phase 1a portion of the trial and reports for BTK-targeted therapies in heavily pretreated patients with B cell malignancies. The presentation by Dr. Abdel-Wahab highlighted critical scientific findings underlying the emergence of new BTK inhibitor resistance mutations that lack BTK’s enzymatic function but still drive tumor growth. These so-call "kinase deficient" and "kinase dead" mutations underscore the importance of BTK’s scaffolding function, which is uniquely addressable by the BTK degrader modality. In the presentation, five different clinically emergent BTK resistance mutations were analyzed and categorized as kinase proficient, kinase deficient, or kinase dead, each conferring a different spectrum of resistance to available therapies. NX-2127 was found to be broadly active against all these mutations. These findings translated into clinically meaningful BTK degradation in the Phase clinical 1 trial and clinical activity independent of baseline BTK mutations.