Nurix Therapeutics, Inc. · NASDAQ:NRIX
Nurix Therapeutics — ASH 2025 (American Society of Hematology annual meeting)
47 slides from Nurix Therapeutics's conference presentation, Dec 9, 2025
Slide 1: Bexobrutideg Clinical Update from ASH 2025
Meeting the Needs of Patients with CLL and WM – Bexobrutideg Clinical Update from ASH 2025 American Society of Hematology December 8, 2025 Exhibit 99.3
Slide 2: Forward-looking statements
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 “anticipate,” “believe,” “could,” “estimat
Slide 3: Nurix pipeline of proprietary and partnered programs
Nurix Is Advancing a Pipeline of Proprietary and Partnered Programs in Oncology and Inflammation & Immunology 3 Program Target Modality Therapeutic area Discovery IND-Enabling Phase 1A Phase 1B/2 Pivotal Bexobrutideg (NX-5948) BTK Degrader B-cell malignancies Zelebrudomide (NX-2127) BTK-IKZF Degrade
Slide 4: Bexobrutideg – The First deg with Potential Best-in-Class Profile
Bexobrutideg – The First “deg” with a Potential Best-in-Class Profile Novel MOA Against a Clinically and Commercially Proven Target 4 Addresses BTK scaffolding function unlike current BTK inhibitors Acts catalytically driving degradation at low free-plasma concentrations Demonstrates robust cl
Slide 5: Bexobrutideg superior mutational coverage and cell killing
Bexobrutideg – The First “deg” with a Potential Best-in-Class Profile Novel MOA Against a Clinically and Commercially Proven Target 5 Addresses BTK scaffolding function unlike current BTK inhibitors Acts catalytically driving degradation at low free-plasma concentrations Demonstrates robust cl
Slide 6: Bexobrutideg – The First deg with Potential Best-in-Class Profile
Bexobrutideg – The First “deg” with a Potential Best-in-Class Profile Novel MOA Against a Clinically and Commercially Proven Target 6 Addresses BTK scaffolding function unlike current BTK inhibitors Acts catalytically driving degradation at low free-plasma concentrations Demonstrates robust cl
Slide 7: One molecule degrades thousands of BTK proteins per hour
Bexobrutideg – The First “deg” with a Potential Best-in-Class Profile Novel MOA Against a Clinically and Commercially Proven Target 7 Addresses BTK scaffolding function unlike current BTK inhibitors Acts catalytically driving degradation at low free-plasma concentrations Demonstrates robust cl
Slide 8: Clinical activity against CLL and NHL in the CNS
Bexobrutideg – The First “deg” with a Potential Best-in-Class Profile Novel MOA Against a Clinically and Commercially Proven Target 8 Addresses BTK scaffolding function unlike current BTK inhibitors Acts catalytically driving degradation at low free-plasma concentrations Demonstrates robust cl
Slide 9: High ORR and prolonged PFS in r/r CLL Phase 1a
Bexobrutideg – The First “deg” with a Potential Best-in-Class Profile Novel MOA Against a Clinically and Commercially Proven Target 9 Addresses BTK scaffolding function unlike current BTK inhibitors Acts catalytically driving degradation at low free-plasma concentrations Demonstrates robust cl
Slide 10: Unlocking a Wave of Clinical Benefit and Value Creation
Unlocking a Wave of Clinical Benefit and Value Creation 10 r/r CLL Accelerated Approval* 2L+ CLL Confirmatory Monotherapy 2L+ CLL Combination Potential 1L+ CLL Combination Bexobrutideg has the potential to create significant value through its broad application across BTK mediated diseases Pivotal DA
Slide 11: Clinical Development Plan to Address Large Segments of the CLL Market
1L Treated: ~61K 2L Treated: ~36K 3L+ Treated: ~24K ~60K treated in R/R CLL Nurix Has a Clinical Development Plan as Both a Mono- and Combo- Therapy to Address Large Segments of the CLL Market 11 1L Treated: ~19K 2L Treated: ~11K 3L+ Treated: ~8K ~19K treated in R/R CLL Major Markets Drug-Treated In
Slide 12: ASH 2025: Two Clinical Updates for Bexobrutideg
ASH 2025: Two Clinical Updates for Bexobrutideg 12 Saturday, December 6, 9:45 a.m. – 10:00 a.m. ET Bexobrutideg (NX-5948), a Novel Bruton’s Tyrosine Kinase (BTK) Degrader, Demonstrates Rapid and Durable Clinical Responses in Relapsed / Refractory Chronic Lymphocytic Leukemia (CLL): New and Updated F
Slide 13: Investor Call Agenda
Investor Call Agenda 13 Bexobrutideg (NX-5948), a Novel Bruton’s Tyrosine Kinase (BTK) Degrader, Demonstrates Rapid and Durable Clinical Responses in Relapsed / Refractory Chronic Lymphocytic Leukemia (CLL): New and Updated Findings from an Ongoing Phase 1a/b Trial Bexobrutideg (NX-5948), a Novel Br
Slide 14: Bexobrutideg demonstrates rapid and durable responses in r/r CLL
Bexobrutideg (NX-5948), a novel Bruton’s tyrosine kinase (BTK) degrader, demonstrates rapid and durable clinical responses in relapsed/refractory chronic lymphocytic leukemia (CLL): New and updated findings from an ongoing Phase 1a/b trial 1Zulfa Omer, 2Alexey Danilov, 3Francesco Forconi, 4Talha Mun
Slide 15: Bexobrutideg Phase 1a/b Trial Design
Bexobrutideg Phase 1a/b (NX-5948-301) Trial Design Phase 1a/b clinical trial in adults with relapsed/refractory B-cell malignancies 15 2L+, second line +; BCL2i, B-cell lymphoma 2 inhibitor; BTKi, Bruton’s tyrosine kinase inhibitor; CLL, chronic lymphocytic leukemia; CNS, central nervous system; NHL
Slide 16: CLL/SLL Patient Disposition
Multiple study cohorts with distinct doses and median follow-up NX-5948-301: CLL/SLL Patient Disposition 16 Data cutoff: 19 Sep 2025 Median follow-up: 9.8 months Safety population (n=42) On treatment (n=29) Randomized cohort (n=42) 200 mg vs 600 mg Other cohorts (n=36) Median follow-up: 19.0 months
Slide 17: CLL/SLL Patient Disposition
Multiple study cohorts with distinct doses and median follow-up NX-5948-301: CLL/SLL Patient Disposition 17 Data cutoff: 19 Sep 2025 Phase 1a/b, all patients – 600 mg (n=70) Median follow-up: 9.8 months Safety population (n=42) On treatment (n=29) Randomized cohort (n=42) 200 mg vs 600 mg Other coho
Slide 18: Demographics in Overall Population (Phase 1a/b)
Demographics in Overall Population (Phase 1a/b) 18 Data cutoff: 19 Sep 2025 Characteristics Phase 1a/b – all patients (n=126) Median age, years (range) 69.0 (35–88) Sex, n (%) Female Male 42 (33.3) 84 (66.7) Ethnicity, n (%) Hispanic or Latino Not Hispanic or Latino Not reported Unknown 5 (4.0) 114
Slide 19: Baseline Disease Characteristics in Phase 1a/b and 1a
Multiple prior lines of therapy and a high prevalence of baseline mutations Baseline Disease Characteristics in Phase 1a/b and 1a aPatients could have received multiple prior treatments; bMutations presented here were centrally sequenced BCL2, B-cell lymphoma 2; BCL2i, BCL2 inhibitor; BTK, Bruton’s
Slide 20: Overall Safety Summary in Phase 1a/b
Tolerable safety profile, consistent between the RP2D 600 mg and overall study population Overall Safety Summary in Phase 1a/b 600 mg Group vs All Patients 20 Phase 1a/b – all patients (n=126) Phase 1a/b 600 mg (n=70) Any TEAE, n (%) 114 (90.5) 60 (85.7) Treatment related 95 (75.4) 51 (72.9) Grade ≥
Slide 21: TEAEs in Phase 1a/b 600 mg Group vs All Patients
Comparable AE profile for patients at the RP2D 600mg dose and overall population TEAEs in ≥10% in Phase 1a/b 600 mg Group vs All Patients 21 Data cutoff: 19 Sep 2025aPurpura/contusion includes episodes of contusion or purpura; bAggregate of ‘neutrophil count decreased’ or ‘neutropenia’; cFatigue was
Slide 22: Reduction in Lymph Node Size in Phase 1a/b
Reduction in Lymph Node Size in Phase 1a/b Overall Populationa Clinical activity across patients with BTK mutations,b high-risk molecular features and/or CNS involvement aWaterfall plot includes patients with measurable lymph node status (n=93); mutations were reported at VAF >5%; bPatients could ha
Slide 23: Overall Response Rate in Phase 1a
Encouraging ORR and long median duration of response Overall Response Rate in Phase 1a Across All Dose Levels (n=47) Response-evaluable patients Phase 1a (n=47) Objective response rate (ORR),a % (95% CI) 83.0 (69.2–92.4) Disease control rate (DCR),b % (95% CI) 95.7 (85.5–99.5) Best response,c n (
Slide 24: Overall Response Rate by Subgroup in Phase 1a
Clinically meaningful response rate observed across difficult-to-treat subgroups Overall Response Rate by Subgroup in Phase 1a (n=47) 24 Data cutoff: 19 Sep 2025aTotal number of response-evaluable patients BCL2i, B-cell lymphoma 2 inhibitor; BTK, Bruton’s tyrosine kinase; BTKi, BTK inhibitor; CI, co
Slide 25: PFS in Phase 1a Across All Dose Levels
PFS in Phase 1a Across All Dose Levels (n=48) PFS summary n=48 Median PFS, months (95% CI) 22.1 (11.2–NE) Median PFS follow-up, months (95% CI) 16.6 (14.0–19.3) Median for PFS by Kaplan–Meier method; median PFS follow-up is by reverse Kaplan–Meier method; 25 Data cutoff: 19 Sep 2025 CI, confidence i
Slide 26: Preliminary Efficacy in Phase 1b Randomized Cohort
Higher ORR and PFS at the RP2D 600 mg dose Preliminary Efficacy in Phase 1b Randomized Cohort of 200 mg vs 600 mg Data cutoff: 19 Sep 2025 26 aObjective response rate includes CR + nPR + PR + PR-L; bDisease control rate includes CR + nPR + PR/PR-L + SD CI, confidence interval; CR, complete response;
Slide 27: Conclusions
Conclusions • In this Phase 1a/b trial, bexobrutideg (NX-5948), a novel BTK degrader with high selectivity for BTK, was well tolerated in a heavily pretreated population of patients with relapsed/refractory CLL/SLL: – Tolerable safety profile consistent with prior disclosures, and consistent between
Slide 28: Patient with CLL with CNS Involvement Showed Deepening Response
28 *Normal spleen: 13 cm; 36-48 week: 13.4 cm The overall response assessments are from the investigators while the individual parameter response assessment criteria are calculated per iwCLL from the data entered ALC, Absolute lymphocyte count; CSF, cerebrospinal fluid; Hgb, hemoglobin; LN, lymph no
Slide 29: Bexobrutideg in Waldenström Macroglobulinemia: Updated Phase 1a/b Results
Bexobrutideg (NX-5948), a Novel Bruton’s Tyrosine Kinase (BTK) Degrader, Shows High Clinical Activity and Tolerable Safety in Patients with Waldenström Macroglobulinemia: Updated Results from an Ongoing Phase 1a/b Study 1Nirav N. Shah, 2Scott Huntington, 3David Lewis, 4Tahla Munir, 5Graham P. Collin
Slide 30: Bexobrutideg Phase 1a/b Trial Design
30 BTKi, Bruton’s tyrosine kinase inhibitor; CNS, central nervous system; DLBCL, diffuse large B-cell lymphoma; FL, follicular lymphoma; MCL, mantle cell lymphoma; MZL, marginal zone lymphoma; NHL, non-Hodgkin’s lymphoma; PCNSL, primary CNS lymphoma; QD, once daily; SCNSL, secondary CNS lymphoma; WM
Slide 31: Baseline demographics/disease characteristics in WM
Baseline demographics/disease characteristics High-Risk WM Population with Extensive Prior Therapy Exposure 31 Characteristics Patients with WM (n=31) Median age, years (range) 71.0 (49–88) Male, n (%) 24 (77.4) ECOG PS, n (%) 0 1 13 (41.9) 18 (58.1) CNS involvement, n (%) 3 (9.7) Median prior lines
Slide 32: Safety Profile Aligns with Prior Clinical Experience
TEAEs in ≥10% of WM population or Grade ≥3 TEAEs in >1 patient Safety Profile Aligns with Prior Clinical Experience Across Indications TEAE, treatment-emergent AE; WM, Waldenstrom’s macroglobulinemia aAggregate of 'neutrophil count decreased' or 'neutropenia’; bPurpura/contusion includes episodes of
Slide 33: High Overall Response Rate in WM Patients
Bexobrutideg overall response assessment (IWWM-6) in patients with WM: Phase 1a/1b High Overall Response Rate in WM Patients Treated with Bexobrutideg CI, confidence interval Primary efficacy analysis All response evaluable patients (n=28)c Exploratory efficacy analysis Patients with ≥2 response ass
Slide 34: Durable Responses Regardless of Prior Therapy or Mutation Status
Durable Responses Regardless of Prior Therapy or Mutation Status (n=31) BTKi, Bruton’s tyrosine kinase inhibitor; BCL2i, B-cell lymphoma 2 inhibitor; MR, minor response; NA, not available; Pirto, pirtobrutinib; PD, progressive disease; PR, partial response; SD, stable disease; VGPR, very good partia
Slide 35: WM conclusions
• Bexobrutideg is a novel small molecule BTK degrader that can overcome treatment-emergent BTKi resistance mutations and disrupt BTK scaffolding. • In the ongoing WM portion of the phase 1 NX-5948-301 study as of the 19 September 2025 data cut: – Median follow-up was 8.1 months, and most patients we
Slide 36: Bexobrutideg: Driving Clinical Momentum and Competitive Leadership
Paula G. O’Connor, M.D. Chief Medical Officer, Nurix Therapeutics Bexobrutideg: Driving Clinical Momentum and Competitive Leadership
Slide 37: Positioned for Success – Recent Key Program Updates
600 mg dose selected per Project Optimus Cleared to move ahead globally (FDA, MHRA, EMA) Pivotal Phase 2 trial initiated – DAYBreak CLL-201 Confirmatory Phase 3 trial initiation planned for H1 2026 New best-in-class in vitro potency and selectivity data Bexobrutideg clinical update at ASH
Slide 38: Current CLL Results Highly Differentiated From Pirtobrutinib
Current CLL Results for Bexobrutideg Are Highly Differentiated From Pirtobrutinib • Bexobrutideg maturing data from Phase 1a in CLL patients demonstrates ORR of 83.0%, median DOR of 20.1 months, and median PFS of 22.1 months • ORR, DOR, and PFS data for bexobrutideg are highly differentiated from pi
Slide 39: Phase 2 Single-Arm Study Designed to Support Accelerated Approval
• Potential to address a current and anticipated future unmet medical need − Pirtobrutinib recently gained full approval • 600 mg cleared for pivotal studies in r/r CLL • First patient dosed in October 2025 Phase 2 Single-Arm Study Designed to Support Accelerated Approval 39 Primary efficacy endpoin
Slide 40: Confirmatory Phase 3 Trial for Full Approval
• Trial designed to support global registrational strategy • Anticipate initiation in H1 2026 • Based on the emerging durability results for bexobrutideg, Nurix believes that bexobrutideg will outperform all components of the investigator’s choice arm 2L+ CLL patients who have been exposed to prior
Slide 41: Phase 1b/2 Combination Study in CLL
Combination regimen of bexobrutideg + BCL-2i maximizes 2L market share opportunity and provides potential path to 1L CLL Phase 1b/2 Combination Study to Address Emerging Treatment Standards in CLL 41 Bexobrutideg + venetoclax 2L+ CLL/SLL Cohort 1 Bexobrutideg + venetoclax + rituximab 2L+ CLL/SLL Coh
Slide 42: Bexobrutideg Clinical Conclusions
CLL • 83% ORR with a 20.1 month median duration of response • Well tolerated with low rate of discontinuation • Progression free survival tracking well above standard of care with a current estimate of 22.1 months WM • 75% ORR, with responses deepening over time including 3 VGPRs • Median duration o
Slide 43: Bexobrutideg and Beyond: Building the Next Generation of TPD Therapies
Arthur T. Sands, M.D., Ph.D. Chief Executive Officer, Nurix Therapeutics Bexobrutideg and Beyond: Building the Next Generation of TPD Therapies
Slide 44: 2025: A Breakthrough Year
2025: A Breakthrough Year as Nurix Hit Several Meaningful Milestones 44 Clinical Execution Excellence • Secured 600mg dose per Project Optimus • Initiated DAYBreak CLL-201 Phase 2 study designed to support Accelerated Approval • Presented compelling update at ASH: 83% ORR and 22.1-month median PFS P
Slide 45: 2026: Accelerating the Next Phase of Leadership in Protein Degradation
2026: Accelerating the Next Phase of Leadership in Protein Degradation 45 1 2 3 Bexobrutideg Phase 1b CLL cohorts Bexobrutideg Phase 1a/b NHL cohorts Bexobrutideg Phase 1 SAD/MAD study Building Evidence with Clinical Data Readouts Advancing Degrader Programs in I&I Executing Pivotal Developmen
Slide 46: Q&A
Q&A (NWuURIX
Slide 47: Nurix
NURIX
Nurix Therapeutics — ASH 2025 (American Society of Hematology annual meeting) on 6ix