Nurix Therapeutics, Inc. · NASDAQ:NRIX
Nurix Therapeutics — 12th International Workshop on Waldenstrom's Macroglobulinemia 2024
17 slides from Nurix Therapeutics's conference presentation, Oct 19, 2024
Slide 1: NX-5948: BTK Degrader with Activity in Lymphoid Malignancies
NX-5948: BTK Degrader with Activity in Lymphoid Malignancies Paula O'Connor, M.D. 12th International Workshop on Waldenstrom’s Macroglobulinemia Prague, Czech Republic October 19, 2024
Slide 2: Important notice and disclaimers
Important notice and disclaimers This presentation contains statements that relate to future events and expectations and as such constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. When or if used in this presentation, the words “anticipa
Slide 3: Nurix Pipeline
Nurix Pipeline Advancing Propriety and Partnered Programs in Oncology and Inflammation & Immunology Oncology Discovery – MOA program Target Therapeutic area Lead Op IND enabling Phase 1a Phase 1b NX-5948 BTK B-cell malignancies TPD NX-2127 BTK-IKZF B-cell malignancies TPE NX-1607 CBL-B Immuno-Oncolo
Slide 4: Rationale for BTK Degraders in WM
Rationale for BTK Degraders in WM • The BCR signaling pathway mediated by BTK is a key driver in oncogenesis and a validated therapeutic target in WM • BTK degraders: – Can overcome treatment-emergent BTK inhibitor resistance mutations1 – Address BTK scaffolding function – the transduction of BCR si
Slide 5: NX-5948 BTK Degrader Mechanism of Action
NX-5948 BTK Degrader Mechanism of Action BTK degraders disrupt BCR signaling by destroying BTK protein and eliminating its immediate and downstream functions NX-5948 BTK Scaffolding References 1. Mo nto ya et al. Kina se-impaire d B TK mutations ar e susceptible to clinical-sta ge BTK an d IKZF1/3 d
Slide 6: NX-5948-301: Trial Design
NX-5948-301: Trial Design Phase 1a/b trial in adults with relapsed/refractory B-cell malignancies Phase 1a dose escalation Potential Phase 1b dose expansion (N = up to 160 patients) CLL/SLL dose A CLL/SLL dose B CLL/SLL 600 mg QD Prior BTKi and BCL2i Prior BTKi and BCL2i (up to 66 patients) 450 mg Q
Slide 7: NX-5948 Safety Summary (All Patients) by Dose
NX-5948 Safety Summary (All Patients) by Dose Frequency of any grade TEAEs in ≥10% of patients or grade ≥3 TEAEs or SAEs in >1 patient Overall population (N=79)1 TEAEs, n (%) Any grade Grade ≥3 SAEs Purpura/contusiona 28 (35.4) – – Thrombocytopeniab 21 (26.6) 7 (8.9) – • 1 DLT (non-protocol mandated
Slide 8: NX-5948 Efficacy: Clinical Response in Patients with CLL
NX-5948 Efficacy: Clinical Response in Patients with CLL Broad antitumor activity in CLL as demonstrated by significant lymph node reduction and ORR CLL disease-evaluable patientsa,1 n=26 Objective response rate (ORR)b, % (95% CI) 69.2 (48.2–85.7) Best response, n (%) CR 0 (0.0) % change from baseli
Slide 9: NX-5948-301: Trial Design
NX-5948-301: Trial Design Phase 1a/b trial in adults with relapsed/refractory B-cell malignancies Phase 1a dose escalation Potential Phase 1b dose expansion (N = up to 160 patients) CLL/SLL dose A CLL/SLL dose B CLL/SLL 600 mg QD Prior BTKi and BCL2i Prior BTKi and BCL2i (up to 66 patients) 450 mg Q
Slide 10: Baseline Demographics/Disease Characteristics
Baseline Demographics/Disease Characteristics Elderly population with multiple prior lines of targeted therapies Patients with WM Characteristics (n=13) Median age, years (range) 74.0 (64–82) Male, n (%) 11 (84.6) ECOG PS, n (%) 0 3 (23.1) 1 10 (76.9) CNS involvement, n (%) 0 Median prior lines of t
Slide 11: NX-5948 BTK degradation
NX-5948 BTK degradation Robust, rapid and sustained degradation across all indications including WM at all dose levels assessed BTK degradation in all BTK degradation in WM patients receiving NX-5948 patients receiving NX-5948 10000 10000 50 mg 300 mg (Background subtracted) 300 mg (Background subtr
Slide 12: NX-5948 Efficacy and Duration of Treatment in Patients with WM
NX-5948 Efficacy and Duration of Treatment in Patients with WM Select prior therapies Select mutations BTKi BCL2i Pirto CXCR4 MYD88 # WM disease-evaluable patients n=9 ORR, % 77.8 Best response, n (%) CR 0 (0.0) PR / MR 7 (77.8) SD 2 (22.2) PD 0 (0.0) * *Ineligible, identified post 1st dose #Transfo
Slide 13: Clinical Case Study 1
Clinical Case Study 1 Patient with WM, MYD88 and CXCR4 mutations, and 4 prior lines of therapy treated with NX-5948 Demographics 64, White, F Treatment outcomes ✓ M spike/paraprotein detectable and decreasing Relevant MYD88mut ✓ No new signs/symptoms of disease mutations CXCR4mut throughout the cour
Slide 14: Clinical Case Study 2
Clinical Case Study 2 Patient with WM, MYD88 mutation, and 3 prior lines of treatment treated with NX-5948 Demographics 66, White, M Treatment outcomes ✓ M spike protein continues to be detectable Relevant ✓ No new signs of disease throughout MYD88mut the course of treatment. mutations ✓ No SAEs, no
Slide 15: Steady Decrease in IgM Levels in Patients Treated with NX-5948
Steady Decrease in IgM Levels in Patients Treated with NX-5948 Percent change in IgM levels from baseline in patients with WM 1 % change from baseline in IgM level # #Transformed to DLBCL 1Response criteria used: Owen RG, Kyle RA, Stone MJ, et al. VIth International Workshop on Waldenström macroglob
Slide 16: Conclusions
Conclusions • NX-5948 is a novel BTK degrader that utilizes the ubiquitin-proteasome pathway to degrade BTK, a well-validated target in B-cell malignancies. BTK degraders: – Can overcome treatment-emergent resistance mutations – Address BTK scaffolding function – Show emerging activity in various B-
Slide 17: Acknowledgments and Next Steps
Acknowledgments and Next Steps • We would like to acknowledge all the patients and investigators for participating in the NX-5948 study • The study plans to enroll into Phase 1b worldwide (USA, UK, Netherlands, Poland, Spain, Italy, France, Switzerland) Active sites Planned sites • The study permits
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