Nurix Therapeutics (NRIX) Study Update summary

Key study highlights

• Bexobrutideg (BexDeg, NX-5948) is a highly selective BTK degrader with potent activity, minimal off-target effects, and only BTK degradation in global proteomics studies.

• Demonstrates ability to overcome resistance mutations seen with BTK inhibitors, maintaining nanomolar potency across all tested mutations.

• Catalytic mechanism allows one drug molecule to degrade up to 10,000 BTK proteins per hour, supporting efficacy at lower doses.

• Achieves CNS penetration, with clinical responses in CNS lymphoma, CLL, and Waldenström macroglobulinemia patients with CNS involvement.

• Robust clinical activity observed, including an 83% overall response rate and median PFS of 22.1 months in phase I-A for CLL.

Clinical trial design and patient population

• Phase I-A/B studies included 126 CLL patients and 31 Waldenström macroglobulinemia patients, with dose escalation from 50 mg to 600 mg and randomized cohorts.

• Median age was 69 for CLL and 71 for Waldenström macroglobulinemia, with most patients heavily pretreated and prior BTK inhibitor exposure.

• Most patients had high-risk mutations and some had CNS involvement at baseline.

• Doses ranged from 200 mg to 600 mg once daily, administered orally.

• Subgroup analysis showed high response rates even in mutation-positive and CNS-involved patients.

Safety and tolerability

• Bexobrutideg was well tolerated, with most adverse events being low grade and manageable.

• No grade 5 toxicities, dose limiting toxicities, or new onset atrial fibrillation observed.

• Neutropenia was the most common grade 3 event, but without infectious complications.

• Two treatment-emergent adverse events led to drug discontinuation.

• No dose-related increase in toxicity up to 600 mg.