Nurix Therapeutics' BTK Degrader NX-5948 Shows Promise in B-Cell Malignancies and Autoimmune Diseases
Key Insights
Nurix Therapeutics' NX-5948 demonstrates a 75.5% objective response rate in relapsed/refractory CLL (search)/SLL (search) patients in Phase 1 study.
NX-5948 receives PRIME designation from EMA for CLL (search) and Fast Track designation from FDA for Waldenstrom's Macroglobulinemia.
Nurix plans to initiate pivotal trials for NX-5948 in CLL (search) and expand development into autoimmune diseases (search) in 2025.
Nurix Therapeutics is advancing NX-5948, an orally bioavailable, brain-penetrant degrader of Bruton’s tyrosine kinase (search) (BTK (search)), showing potential in treating B-cell malignancies (search) and autoimmune diseases (search). The company presented positive data from the Phase 1 clinical trial of NX-5948 at the 66th American Society of Hematology (ASH) Annual Meeting in December 2024, demonstrating a robust objective response rate (ORR) of 75.5% in patients with relapsed/refractory chronic lymphocytic leukemia (search)/small lymphocytic lymphoma (search) (r/r CLL (search)/SLL (search)). These results pave the way for potential global registration trials in 2025.
Clinical Trial Results and Regulatory Designations
The Phase 1 trial data presented at ASH2024 included 49 efficacy-evaluable r/r CLL (search)/SLL (search) patients across all doses tested. The majority of responses occurred at the first assessment (Week 8), with the ORR increasing to 84.2% in patients with at least two response assessments (Week 16). Responses and robust BTK (search) degradation were observed across all populations regardless of prior treatment, baseline mutations, high-risk molecular features, or central nervous system (CNS) involvement. The drug was well-tolerated across all patient populations and doses (50 to 600 mg daily).
In addition to the promising clinical data, NX-5948 has received significant regulatory designations. The U.S. Food and Drug Administration (search) (FDA) granted Fast Track designation for NX-5948 in both r/r CLL (search)/SLL (search) and Waldenstrom’s Macroglobulinemia (search) (WM (search)). The European Medicines Agency (search) (EMA) granted PRIME designation for NX-5948 in CLL. These designations are designed to expedite the development and review of drugs that treat serious conditions and fill unmet medical needs.
Expansion into Autoimmune Diseases
Beyond its potential in B-cell malignancies (search), Nurix is also exploring the development of NX-5948 in autoimmune and inflammatory diseases. Preclinical data presented at the American College of Rheumatology (ACR) Convergence 2024 demonstrated that NX-5948 achieves deep suppression of BCR, TLR, and FcR signaling in immune cells and demonstrates efficacy in preclinical models of arthritis and other inflammatory diseases. Nurix plans to initiate clinical testing of NX-5948 in autoimmune cytopenias (search), such as warm autoimmune hemolytic anemia (search) (wAIHA (search)), in 2025, initially as an addition to its ongoing Phase 1b trial in patients with B-cell malignancies.
Other Pipeline Developments
Nurix is also advancing other programs in its pipeline, including:
- NX-2127: An orally bioavailable degrader of BTK and the cereblon neosubstrates IKZF1 (Ikaros) and IKZF3 (Aiolos) for the treatment of relapsed or refractory B-cell malignancies. Enrollment in the Phase 1 trial has been re-initiated with new, chirally controlled drug product.
- NX-1607: An orally bioavailable inhibitor of the E3 ligase Casitas B-lineage lymphoma proto-oncogene B (CBL-B) for immuno-oncology indications. It is currently being evaluated in a Phase 1 trial in monotherapy and in combination with paclitaxel.
- GS-6791 (previously NX-0479): A potent, selective, oral degrader of IRAK4 being developed in collaboration with Gilead for rheumatoid arthritis and other inflammatory diseases. Gilead is responsible for IND-enabling studies and clinical development, anticipated in 2025.
- STAT6 degrader: A program in collaboration with Sanofi for the development of a degrader of STAT6, a key drug target in type 2 inflammation, with the goal of nominating a development candidate in the first half of 2025.
Financial Position
Nurix Therapeutics is well-capitalized, with cash and marketable securities of $609.6 million as of November 30, 2024. This strong financial position enables the company to aggressively develop NX-5948 in multiple indications and advance its wholly owned and collaboration programs.
According to Arthur T. Sands, M.D., Ph.D., president and chief executive officer of Nurix, the company has "hit the ground running in 2025 with plans to commence a suite of clinical trials designed to support global registration of NX-5948 for the treatment of patients with CLL (search) and to explore its development in inflammatory diseases."