Nurix Therapeutics Advances Bexobrutideg Toward Pivotal CLL Trials with Strong Phase 1 Data
核心洞察
Nurix Therapeutics announced plans to initiate pivotal trials for bexobrutideg (搜索) in relapsed/refractory chronic lymphocytic leukemia (搜索) patients in the second half of 2025, including both accelerated approval and confirmatory Phase 3 studies.
Phase 1a data presented at SOHO 2025 demonstrated bexobrutideg (搜索) achieved an 80.9% objective response rate in 47 CLL patients, with rapid responses and durable activity across high-risk subgroups including those with TP53, PLCG2, and BTK (搜索) mutations.
The BTK (搜索) degrader showed strong efficacy in Waldenström macroglobulinemia (搜索) with an 84.2% response rate in 19 patients, while maintaining a favorable safety profile with no dose-limiting toxicities or atrial fibrillation events.
Nurix Therapeutics is preparing to advance its lead BTK (搜索) degrader bexobrutideg (搜索) into pivotal trials for chronic lymphocytic leukemia (搜索) (CLL) following encouraging Phase 1 results that demonstrated high response rates and favorable tolerability across challenging patient populations.
The San Francisco-based biopharmaceutical company announced plans to initiate a single-arm study for potential accelerated approval in relapsed/refractory CLL patients in the second half of 2025, alongside a randomized controlled Phase 3 trial comparing bexobrutideg (搜索) to investigator's choice control arms including bendamustine and rituximab, idelalisib and rituximab, or pirtobrutinib.
Strong Clinical Performance Across Blood Cancers
At the Society of Hematologic Oncology (SOHO) 2025 Annual Meeting in September, Nurix presented encore Phase 1a data for bexobrutideg (搜索) in relapsed or refractory CLL patients. Among 47 response-evaluable patients, the BTK (搜索) degrader achieved an objective response rate (ORR) of 80.9%, including one complete response.
The responses demonstrated rapid onset, with a median time to first response of 1.9 months, and continued to deepen with longer treatment duration. Notably, durable activity was observed across high-risk patient subgroups, including those harboring TP53, PLCG2, and BTK (搜索) mutations, as well as patients with central nervous system involvement.
"These results support advancement of bexobrutideg (搜索) into pivotal studies planned to initiate in the second half of 2025," the company stated, highlighting the drug's potential to address treatment-resistant disease.
In Waldenström macroglobulinemia (搜索) (WM), bexobrutideg (搜索) demonstrated similarly impressive efficacy. Among 19 response-evaluable patients with relapsed or refractory disease, the drug achieved an ORR of 84.2%, with responses observed across patients harboring MYD88 and CXCR4 mutations. Responses were rapid, durable, and associated with deep reductions in serum IgM levels.
Favorable Safety Profile Supports Development
The safety profile of bexobrutideg (搜索) has been consistently favorable across both indications. The drug was well tolerated with no dose-limiting toxicities reported and notably, no new cases of atrial fibrillation or flutter—a significant advantage over existing BTK (搜索) inhibitors that carry cardiovascular risks.
"These findings underscore the potential of BTK (搜索) degraders to overcome BTKi resistance and provide meaningful benefit to heavily pretreated WM patients," Nurix noted in its clinical update.
Expanding Pipeline and Strategic Collaborations
Beyond bexobrutideg (搜索), Nurix is advancing multiple programs through strategic partnerships. At the European Academy of Dermatology and Venereology (EADV) 2025 Congress, the company and collaboration partner Gilead Sciences presented preclinical findings for GS-6791, a novel, selective oral IRAK4 (搜索) degrader.
The preclinical data demonstrated potent degradation of IRAK4 (搜索) in immune and epithelial cells, effectively blocking IL-1 and IL-36 signaling pathways implicated in autoimmune and inflammatory diseases. In vivo studies showed GS-6791 suppressed cytokine production and improved disease measures in a mouse model of dermatitis (搜索).
"The data highlight the differentiated mechanism of IRAK4 (搜索) degradation compared with kinase inhibition and support the potential of GS-6791 to deliver efficacy across a range of inflammatory conditions," according to the company's presentation.
GS-6791 is currently in healthy volunteer studies, while Nurix and Sanofi continue to advance the STAT6 degrader NX-3911 (搜索) in IND-enabling studies.
Financial Position Supports Clinical Acceleration
Nurix reported cash, cash equivalents and marketable securities of $428.8 million as of August 31, 2025, providing substantial financial runway for its clinical programs. However, research and development expenses increased significantly to $86.1 million in the third quarter of 2025, compared to $55.5 million in the same period of 2024.
The increase was primarily attributed to clinical, contract manufacturing and consulting costs as the company accelerated patient enrollment in the ongoing bexobrutideg (搜索) trial and prepared for pivotal trial initiation.
"Nurix is preparing to initiate pivotal studies for bexobrutideg (搜索) in relapsed/refractory CLL patients in the fourth quarter of 2025," said Arthur T. Sands, M.D., Ph.D., president and chief executive officer of Nurix. "With a strong wholly owned pipeline and world-class partnerships, Nurix is well positioned to establish degrader-based medicines as a new standard of care in both cancer and autoimmune diseases."
Broader Development Strategy
The company is also exploring bexobrutideg (搜索)'s potential in autoimmune and inflammatory diseases, enrolling a Phase 1b cohort for patients with CLL and autoimmune hemolytic anemia (搜索). Nurix is conducting Phase 1 healthy volunteer studies to support a potential autoimmune indication filing in 2026.
Additional pipeline assets include zelebrudomide, an orally bioavailable degrader targeting BTK (搜索) and cereblon neosubstrates IKZF1 (搜索) and IKZF3 (搜索) for B-cell malignancies, and NX-1607, an oral CBL-B (搜索) inhibitor being developed for immuno-oncology indications across solid tumors and lymphomas.