Nurix Therapeutics, a biopharmaceutical company focused on targeted protein modulation, announced the expansion of the Phase 1b clinical trial for NX-5948, an investigational, orally bioavailable degrader of Bruton's tyrosine kinase (BTK), in patients with relapsed or refractory B-cell malignancies. The trial includes patients with chronic lymphocytic leukemia (CLL), Waldenstrom’s macroglobulinemia (WM), marginal zone lymphoma, and follicular lymphoma. This expansion follows the FDA's Fast Track designation for NX-5948 in CLL, a patient population that has been treated with at least two prior regimens, including a BTK inhibitor and a BCL2 inhibitor.
NX-5948 Clinical Development
The Phase 1b portion of the trial randomizes patients to either a low dose (200mg QD) or a high dose (600mg QD) of NX-5948. Nurix plans to present additional clinical data from the CLL study by the end of 2024 and a clinical update on the WM study at the 12th International Workshop on Waldenstrom’s Macroglobulinemia (IWWM 12) later this month. A Phase 1 healthy volunteer study is also underway to assess food effects and drug-drug interactions, with pivotal development planned for 2025.
Nurix is also exploring NX-5948 for autoimmune and inflammatory diseases, with preclinical studies expected to enable an investigational new drug (IND) application in autoimmune indications. Data will be presented at the upcoming annual meeting of the American College of Rheumatology (ACR 2024) in Washington, D.C., showcasing the drug's efficacy in preclinical models of arthritis and other inflammatory diseases.
NX-2127 Trial Reinitiation
Enrollment has been reinitiated in the Phase 1a/b clinical trial of NX-2127, an orally bioavailable BTK degrader that also degrades cereblon neosubstrates IKZF1 (Ikaros) and IKZF3 (Aiolos), for the treatment of relapsed or refractory B-cell malignancies. The trial includes Phase 1b expansion cohorts focused on patients with diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL). Nurix has introduced a new chirally controlled drug product, which is being evaluated in a dose escalation study within this trial. Clinical updates are anticipated in 2025.
Degrader-Antibody Conjugates (DACs)
Nurix presented early preclinical data from its ongoing collaboration with Pfizer to develop Degrader-Antibody Conjugates (DACs) at the ADC & Radiopharmaceuticals Pharma & Biotech Partnering Summit on September 10, 2024. DACs combine the catalytic activity of a targeted protein degrader with the tissue specificity of an antibody, potentially providing an improved therapeutic index and broader applicability than standard antibody-drug conjugates (ADCs).
