Nurix Therapeutics (NRIX) investor relations material

Key study findings

• Bexobrutideg (BexDeg) is a highly selective BTK degrader with strong molecular selectivity, potent activity against all known BTK resistance mutations in CLL, robust CNS penetration, and minimal off-target effects, leading to responses in CNS-involved disease.

• In phase I-A/B studies for CLL, 126 patients (median age 69) were treated, many with high-risk features and prior BTK/BCL2 inhibitor exposure; 83% overall response rate (ORR) and 22-month median progression-free survival (PFS) were observed, including responses in heavily pretreated and CNS-involved patients.

• In Waldenstrom's macroglobulinemia, 31 patients (median age 71, median three prior therapies) showed a 75–83% ORR and 60–70% major response rate, including responses in patients with CNS involvement and prior BTK inhibitor exposure; responses were durable, with 14 patients on treatment over six months and six over one year.

• Responses occurred regardless of MYD88 or CXCR4 mutation status, and disease control rate reached 100% in patients with two or more assessments.

• Responses were rapid and deepened over time, with activity seen across all mutational subgroups and no significant difference in response kinetics by mutation; 600 mg was established as the recommended phase II dose.

Safety and tolerability

• Bexobrutideg was well tolerated, with most adverse events being grade 1/2; neutropenia was the most common grade 3 event, and no grade 5 toxicities or dose-limiting toxicities were observed.

• Most common adverse events included neutropenia, petechiae, diarrhea, anemia, purpura/contusion, and thrombocytopenia.

• No new or unexpected adverse events emerged at higher doses, and no new onset atrial fibrillation was reported.

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

• Safety profile was similar in CLL and Waldenstrom's macroglobulinemia.

Study design and patient population

• Phase 1 trial in Waldenstrom's included 31 patients (median age 71, median three prior therapies), all with prior BTK inhibitor exposure; doses ranged from 200 mg to 600 mg once daily.

• Three patients had CNS involvement at baseline, with two responding to treatment.

• Subgroup analysis showed high response rates even in heavily pre-treated and mutation-positive patients.

• In CLL, 126 patients (median age 69) were treated, many with high-risk features and prior BTK/BCL2 inhibitor exposure.

• Responses were observed in both CLL and Waldenstrom's patients with CNS involvement.