Nurix Therapeutics presents clinical data from NX-5948, NX-2127 programs

Nurix Therapeutics presented clinical data from its orally available degraders of BTK, NX-5948 and NX-2127, which are being evaluated in separate Phase 1a/1b clinical trials in patients with relapsed or refractory B-cell malignancies, including CLL, mantle cell lymphoma, diffuse large B-cell lymphoma, marginal zone lymphoma, follicular lymphoma, primary CNS lymphoma, and Waldenstrom’s macroglobulinemia. These data were presented in two posters at the 65th American Society of Hematology Annual Meeting and Exposition, which is being held in San Diego, California. Nurix reported data from the dose escalation stage of its Phase 1a/1b clinical trial evaluating daily oral dosing of BTK degrader NX-5948 in patients with r/r B-cell malignancies. These data were from 26 patients enrolled in cohorts 1-5 who had received a median of four prior therapies and included patients with acquired mutations associated with drug resistance. Dose-dependent pharmacokinetics were observed, resulting in rapid, robust, and sustained BTK degradation in all patients treated once daily with oral NX-5948. In the CLL population that received doses ranging from 50 to 200 mg, six of seven patients demonstrated clinical benefit with three partial responses that were all ongoing as of the October 17, 2023 data cut, including one over nine months and three showing stable disease, with treatment ongoing in two patients. In NHL patients who were treated with doses from 50 to 450 mg, durable responses were seen across indications, with almost half the patients continuing to receive treatment as of the cut-off date. NX-5948 was well-tolerated across all doses tested with no dose limiting toxicities or treatment-related serious adverse events and no treatment emergent adverse events that resulted in drug discontinuation. Importantly, there were no incidences of atrial fibrillation or hypertension. Dose escalation continues across all indications and the study is actively enrolling patients in the United States, the United Kingdom, and the Netherlands. Additional data with higher dose levels and longer treatment duration are expected in 2024.Data from the Phase 1a dose escalation and Phase 1b dose expansion cohorts of Nurix’s clinical trial of NX-2127, an orally available degrader of both BTK and cereblon neosubstrates Ikaros and Aiolos were reported in a second poster presentation. The presentation included data from 54 patients with r/r B-cell malignancies treated once daily with NX-2127 at doses that ranged from 100 to 300 mg. The patient population had a median age of 72.5 years and had received a median of four prior lines of therapy. Among the patients with CLL, 36% had acquired BTK mutations associated with BTK inhibitor drug resistance prior to entry in the study. NX-2127 exhibited dose-dependent PK, leading to robust and sustained degradation of BTK and biologically-relevant degradation of Ikaros. Treatment with NX-2127 resulted in encouraging rapid and durable responses in this heavily pre-treated patient population with complete responses reported in two of the 17 evaluable NHL patients. These responses were durable for over one year. Two PRs in other NHL patients were also reported. Among the 27 evaluable patients with CLL, 11 experienced a PR for an overall response rate of 40.7%. This compares favorably to earlier results presented at ASH 2022 showing a preliminary 33% ORR. NX-2127 had a manageable safety profile that was consistent with previous reports for BTK-targeted and immunomodulatory therapies. The most common grade greater than or equal to3 TEAEs were neutropenia, which showed evidence of dose response, hypertension and anemia. Atrial fibrillation was observed in six patients, with three patients having grade greater than or equal to3 events. Twenty-one patients had serious TEAEs, of which eight had serious adverse events considered related to NX-2127 treatment. Two patients experienced DLTs, and 13 patients developed TEAEs that resulted in discontinuation of NX-2127. As of the September 15, 2023 cutoff date, treatment was ongoing in 13 patients.