Nurix BTK degrader bexobrutideg shows 92.9% ORR in second-line CLL
Nurix Therapeutics has released updated clinical data for bexobrutideg (NX-5948), its investigational oral BTK degrader, showing high response rates across multiple lines of therapy in chronic lymphocytic leukaemia. The results were presented during an oral session at the European Hematology Association Congress in Stockholm on 11 June 2026.
The headline figure from the Phase 1b expansion cohorts is a 92.9% objective response rate among evaluable patients in Cohort 5, comprising patients who had previously received a BTK inhibitor but had not been treated with a BCL2 inhibitor. Eighteen of 19 patients in that cohort remained on treatment at the January 2026 data cutoff, though median follow-up was still early at 5.2 months.
Phase 1a: durable responses in heavily pretreated patients
The longer-established Phase 1a dataset, drawn from 48 relapsed or refractory CLL and SLL patients with a median of four prior lines of therapy, continues to mature. At a median follow-up of 22.4 months, bexobrutideg produced a median progression-free survival of 22.1 months (95% CI: 14.0 to not reached) and an objective response rate of 83.0% (95% CI: 69.2 to 92.4). Responses were observed in patients carrying BTK inhibitor resistance mutations, TP53 mutations and, notably, in those with CNS involvement, a subgroup that is historically difficult to treat with agents that do not cross the blood-brain barrier.
Across all 142 Phase 1a/b CLL patients, the safety profile remained consistent with prior disclosures. No dose-limiting toxicities were recorded, no treatment-related Grade 5 adverse events occurred, and treatment discontinuation due to adverse events was reported in only 5.6% of patients. The most common treatment-emergent adverse events were purpura or contusion, neutropenia, petechiae, diarrhoea and fatigue.
Competitive landscape and regulatory path
Paula O'Connor, chief medical officer of Nurix, said the durability of responses in heavily pretreated patients combined with promising activity in BCL2i-naïve and BTKi-naïve cohorts supports the case for bexobrutideg across all lines of therapy.
The BTK space in CLL is already crowded, with covalent inhibitors such as ibrutinib and acalabrutinib widely used and second-generation non-covalent agents including zanubrutinib and pirtobrutinib competing for market share. Bexobrutideg is differentiated by its mechanism as a targeted protein degrader rather than an inhibitor, and by its CNS penetrance, which could give it an edge in patients with CNS involvement or with resistance mutations that reduce binding affinity for conventional inhibitors. Whether degradation translates to a clinically meaningful advantage in head-to-head settings remains to be demonstrated in randomised trials.
Nurix said it intends to advance a broad Phase 3 monotherapy programme and is exploring combination regimens in first- and second-line settings. Those plans are being developed alongside Roche, which entered into a collaboration agreement with Nurix announced earlier this year. The pivotal single-arm Phase 2 DAYBreak CLL-201 study is already enrolment-active, and a new tablet formulation is being tested in a first-in-human study targeting future immunology and neurology applications, extending the potential addressable market well beyond haematological malignancies.
Talha Munir, consultant haematologist at Leeds Teaching Hospitals NHS Trust and deputy chair of the UK National Cancer Research Institute CLL Study Group, said responses were observed across patients with difficult-to-treat disease characteristics including resistance mutations, high-risk molecular features and CNS involvement, while the tolerability profile remained favourable.