Nurix Therapeutics (NRIX) Study Update summary

Key clinical results

• NX-5948 achieved a 69.2% objective response rate in 26 evaluable, heavily pretreated CLL patients, including those with BTK resistance mutations and CNS involvement, with rapid, deepening, and durable responses observed as early as 8 weeks.

• Responses included patients with poor prognostic features such as TP53 and BTK mutations, and were ongoing at data cutoff, with many patients remaining on treatment for over 10 cycles.

• Activity was seen across all dose levels and in patients with CNS involvement, including near-complete response and CSF clearance in a CNS patient by 24 weeks.

• Responses were observed regardless of prior exposure to covalent and non-covalent BTK inhibitors.

• NX-5948 induced rapid and robust degradation of both wild-type and mutant BTK, overcoming resistance from various BTK mutations.

Patient population and study design

• The phase 1a/1b trial enrolled 79 patients (31 with CLL), most elderly and heavily pretreated (median age 67, median 4 prior therapies), with high prevalence of prior BTK inhibitor exposure and poor-prognosis mutations.

• High-risk features were common: 45% had BTK mutations, many had TP53 mutations, and 15% had prior CNS involvement.

• The study included dose escalation (50–600 mg daily) and planned expansion to up to 150 patients in phase 1b.

• The trial included adults with relapsed/refractory B-cell malignancies, including CLL, SLL, NHL, and WM.

Safety and tolerability

• NX-5948 was well tolerated, with most common adverse events being purpura/contusion, thrombocytopenia, neutropenia, and fatigue, often pre-existing.

• No dose reductions or discontinuations due to toxicity in CLL; two inadvertent dose reductions were unrelated to safety.

• Only one dose-limiting toxicity and two treatment-emergent adverse events led to discontinuation; no new safety signals at higher doses.

• No new cardiac or CNS safety signals observed; one grade 5 event (pulmonary embolism) was not drug-related.

• Safety profile compares favorably to first- and second-generation BTK inhibitors, with less cardiac toxicity.