Nurix Therapeutics, Inc. · NASDAQ:NRIX
Nurix Therapeutics — 7th Annual TPD & Induced Proximity Summit 2024
20 slides from Nurix Therapeutics's conference presentation, Oct 30, 2024
Slide 1: Clinical Activity of NX-5948: A First-in-Class BTK Degrader
Clinical Activity of NX-5948: A First-in-Class BTK Degrader Paula O'Connor, M.D. Chief Medical Officer 7TH Annual TPD & Induced Proximity Summit 2024 Boston, MA October 30, 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 Is Advancing a Pipeline of Proprietary and Partnered Programs
Nurix Is Advancing a Pipeline of Proprietary and Partnered Programs in Oncology and Inflammation & Immunology Discovery – IND Program Target MOA Therapeutic area Phase 1a Phase 1b Lead Op enabling NX-5948 BTK TPD B-cell malignancies NX-2127 BTK-IKZF TPD B-cell malignancies NX-1607 CBL-B TPE Immuno-O
Slide 4: Rationale for BTK Degraders
Rationale for BTK Degraders • The BCR signaling pathway mediated by BTK is a key driver in oncogenesis and a validated therapeutic target in multiple lymphoid malignancies • BTK degraders: – Can overcome treatment-emergent BTK inhibitor resistance mutations1,2 – Address BTK scaffolding function – th
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. Montoya et al. Kinase-impaired BTK mutations are susceptible to clinical-stage BTK and IKZF1/3 degrader
Slide 6: NX-5948-301: Trial Design
NX-5948-301: Trial Design Phase 1a/b trial in adults with relapsed/refractory B-cell malignancies: Now enrolling Phase 1b 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
Slide 7: Baseline Demographics/Disease Characteristics
Baseline Demographics/Disease Characteristics Elderly population with multiple prior lines of targeted therapies and poor prognosis mutations Overall population Patients with CLL Patients with WM Characteristics (N=79) (n=31) (n=13) Median age, years (range) 67.0 (35–88) 69.0 (35–88) 74.0 (64–82) Ma
Slide 8: NX-5948 Is Well Tolerated with Limited Adverse Events Leading to Discontinuation
NX-5948 Is Well Tolerated with a Limited Number of Adverse Events Leading to Drug Discontinuation 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) – – Thrombocytopenia
Slide 9: NX-5948 BTK Degradation
NX-5948 BTK Degradation Robust, rapid and sustained degradation independent of BTK mutation status All Patients (N=75) (n=28) CLL Patients (N=28) 10000 10000 (Background subtracted) 300 mg (Background subtracted) 50 mg Wild type (n=15) 8000 100 mg 450 mg 8000 BTK T474F/I (n=3) Mean ± SEM Mean±SEM 20
Slide 10: NX-5948 Efficacy (Response-Evaluable Patients with CLL)
NX-5948 Efficacy (Response-Evaluable Patients with CLL) ORR assessment includes patients whose responses deepened over time CLL disease-evaluable patientsa n=26 Objective response rate (ORR)b, % (95% CI) 69.2 (48.2–85.7) Best response, n (%) CR 0 (0.0) * Patient with Richter’s Transformation (RT) to
Slide 11: Clinical Activity in Patients with Baseline Mutations
Clinical Activity in Patients with Baseline Mutations No genotypic profile linked to intrinsic NX-5948 resistance • Baseline treatment-resistance and poor prognosis mutations were common, indicating a genetically diverse and hard- to-treat CLL patient population • No genotypic profile was linked to
Slide 12: NX-5948 Duration of Treatment
NX-5948 Duration of Treatment Durable responses, including responses beyond one year in heavily pretreated patients with CLL Select prior therapies ≥2 prior BCL2i cBTKi ncBTKi BTKi 1 year on treatment Median duration of treatment, months (range) 2.8 (0.2–15.2) Patients dose escalated during treatmen
Slide 13: Case Study 1: Patient with CLL and CNS Involvement
Case Study 1: Patient with CLL and CNS Involvement Relevant medical history Age, Race, M/F 59, White, M • Anxiety: 2015-ongoing Diagnosis CLL, High Risk, Stage C • Depression: 2015-ongoing • Previous Hepatitis B infection: 2015 (on anti-viral prophylaxis but Initial diagnosis May 2015 no evidence of
Slide 14: Case Study 1: Patient with CLL and CNS Involvement
Case Study 1: Patient with CLL and CNS Involvement Deepening response over time approaching complete response criteria 8 weeks: Stable Disease 36 weeks: Partial Response LN: –53% (>50% PR) LN: all <1.5 cm (CR) 60 Spleen: –13% (–49% to +49% SD) Spleen: –87% (>50% PR)* ALC Plts: >100 (CR) Plts: >100 (
Slide 15: Case Study 2: CLL Patient Exposed to CIT, cBTKi, BCL2i, and PI3Ki
Case Study 2: CLL Patient Exposed to CIT, cBTKi, BCL2i, and PI3Ki Relevant medical history Age, M/F 66, M • Supraventricular tachycardia: Jun 2018 - present • Peripheral neuropathy: Oct 2018 - present Diagnosis CLL • Hearing loss: Apr 2008 - present • Tinnitus: Apr 2008 - present Initial diagnosis 2
Slide 16: Case Study 2: CLL Patient Exposed to CIT, cBTKi, BCL2i, and PI3Ki
Case Study 2: CLL Patient Exposed to CIT, cBTKi, BCL2i, and PI3Ki Early clinical activity deepening over time 180 Baseline LN SPD: 8522 cm2 Spleen*: 18.9 cm 160 ALC: 130 x 109/L Plts: 242 x 109/L 140 8 weeks: Partial Response Hgb: 8 g/dL LN: –59% ( >50% PR) Spleen: –68% (>50% PR) Cell Counts (K/µL)
Slide 17: NX-5948 Duration of Treatment in Patients with Waldenstrom's Macroglobulinemia
NX-5948 Duration of Treatment in Patients with Waldenstrom’s Macroglobulinemia Durable responses, over 1 year, seen in pretreated patients with at least 2 prior therapies (BTKi and chemo-immunotherapy) Select prior therapies Select mutations BTKi BCL2i Pirto CXCR4 MYD88 # WM disease-evaluable patien
Slide 18: 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 Waldenström’s macroglobulinemia1 % change from baseline in IgM level # #Transformed to DLBCL 1Response criteria used: Owen RG, Kyle RA, Stone MJ, et al. VIth International Works
Slide 19: 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 • In an ongoing Phase 1 clinical trial (n=79), NX-5948 has demonstrated a tolerable safety profile as of the April 17, 2024 data cut: – Safety p
Slide 20: Acknowledgments and Next Steps
Acknowledgments and Next Steps • We would like to acknowledge all the patients and their families, as well as 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 Planne
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