Nurix Therapeutics, Inc. · NASDAQ:NRIX
Nurix Therapeutics — Investor Presentation (October 2025)
53 slides from Nurix Therapeutics's investor presentation, Oct 22, 2025
Slide 1: Bexobrutideg Investor Update
Bexobrutideg Investor Update Investor Presentation October 2025
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 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: Targeted Protein Degradation: A Leader in the Next Frontier in Drug Development
Targeted protein degradation (TPD) A Leader in the Next Frontier in Drug Development 4 Evolution of new therapeutic modalities AntibodiesSmall molecule inhibitors Nucleic acid-based therapies (Antisense, RNAi Gene Therapy, CRISPR) Targeted protein degraders
Slide 5: Positioned for Success – 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 data New proteomics highlighting best-in-class selectivi
Slide 6: Bexobrutideg – The First "deg" with a 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 Demonstrated robust cl
Slide 7: Agenda
Agenda 7 Q&A to follow Paula G. O’Connor, M.D. Chief Medical Officer Bexobrutideg Clinical Development Update Gwenn Hansen, Ph.D. Chief Scientific Officer Best-in-Class BTK Degrader: Potency, Coverage, and Selectivity Extending our leadership into I&I
Slide 8: DAYBreak: Registrational Pathway for Bexobrutideg in R/R CLL
Paula G. O’Connor, M.D. Chief Medical Officer DAYBreak: Registrational Pathway for Bexobrutideg in R/R CLL
Slide 9: Bexobrutideg 600 mg Once Daily Oral Dose Cleared by Global Regulators
Bexobrutideg 600 mg Once Daily Oral Dose Cleared by Global Regulators for Pivotal Monotherapy Trials in Relapsed/Refractory CLL • Highest dose tested in Phase 1 cleared by global regulators for pivotal monotherapy studies in r/r CLL – U.S. Food and Drug Administration (FDA), in accordance with Proje
Slide 10: Bexobrutideg Has Consistently Demonstrated Strong Clinical Activity
Bexobrutideg Has Consistently Demonstrated Strong Clinical Activity 10 Efficacy Data Across All Patients Efficacy Data Per Patient Regardless of Mutations or High Risk Cytogenetic Features CLL response-evaluable patientsa Response analysis (n=47) Objective response rate (ORR),b % (95% CI) 80.9 (66.7
Slide 11: Bexobrutideg Demonstrates Durable Responses in Relapsed/Refractory CLL
Bexobrutideg Demonstrates Durable Responses in Patients with Relapsed/Refractory CLL (n=48) BCL2i, BCL2 inhibitor; BTKi, BTK inhibitor; cBTKi, covalent BTKi; CI, confidence interval; CIT, chemo/chemo-immunotherapies; CR, complete response; ncBTKi, non-covalent BTKi; NE, not evaluable; NR, not reache
Slide 12: Bexobrutideg Safety Profile: Well Tolerated in Relapsed/Refractory CLL
Bexobrutideg Safety Profile: Well Tolerated in Patients with Relapsed/Refractory CLL 12 TEAEs, n (%) Patients with CLL/SLL (n=48) Any grade Grade ≥3 SAEs Purpura/contusiona 22 (45.8) – – Diarrhea 15 (31.3) 2 (4.2) – Fatigueb 15 (31.3) – – Neutropeniac 14 (29.2) 11 (22.9) – Rashd 13 (27.1) 1 (2.1) 1
Slide 13: Phase 2 Single-Arm Study for Potential Accelerated Approval
• Accelerated approval strategy depends on: − FDA’s determination of unmet need at time of regulatory review − Adequate enrollment in confirmatory Phase 3 trial • Trial designed to support potential accelerated approval in a high unmet need treatment setting − Post-cBTKi, post-ncBTKi, and post-BCL-2
Slide 14: Confirmatory Phase 3 Trial for Full Approval
• Single trial strategy to support global approval • Investigator’s choice control arm: − Provides clinical relevance across geographies − Addresses current and emerging standards of care − Maximizes enrollment opportunities − Provides option for cross over to bexobrutideg upon documented progressio
Slide 15: Phase 1b/2 Combination Study to Address Emerging Treatment Standards 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 15 Bexobrutideg + venetoclax 2L+ CLL/SLL Cohort 1 Bexobrutideg + venetoclax + rituximab 2L+ CLL/SLL Coh
Slide 16: Building a World Class Hematology/Oncology Franchise
• Phase 2 DAYBreak trial underway for monotherapy in r/r CLL • Confirmatory Phase 3 for monotherapy in r/r CLL planned to start in H1 2026 • Combination trial planned to start H1 2026 to expand clinical opportunity across lines of therapy in CLL – Initial focus on combinations with standards of care
Slide 17: Potential Best-in-Class BTK Degrader: Potency, Coverage, and Selectivity
Gwenn Hansen, Ph.D. Chief Scientific Officer Potential Best-in-Class BTK Degrader: Potency, Coverage, and Selectivity
Slide 18: Bexobrutideg – Defining a Best-in-Class Profile
Bexobrutideg – Defining a Best-in-Class Profile 18 Best-in-class mutational coverage Best-in-class degrader selectivity Best-in-class degrader potency FDA clearance to proceed with highest tested dose BTK, Bruton's tyrosine kinase; CNS, central nervous system Clear evidence of clinical act
Slide 19: Bexobrutideg Displays Best-in-Class BTK Degradation Potency
Bexobrutideg Displays Best-in-Class BTK Degradation Potency Degradation assessed at 24 hours by flow cytometry in human peripheral blood mononuclear cells, gated on CD20+ B cells AbbVie cmpd. 1 is example 1 from WO 2023/183811 A119 Bexobrutideg is 20x more potent than BGB-16673 and 5x more potent th
Slide 20: Bexobrutideg Degrades Wild-Type and Mutated BTK with Superior Coverage
Bexobrutideg Degrades Wild-Type and Mutated BTK with Superior Coverage Compared to All BTK Inhibitors BTK, Bruton’s tyrosine kinase; GI-50 growth inhibition 50%; WT wildtype20 Bexobrutideg shows superior mutational coverage and cell killing compared to BTK inhibitors Most potent cell killing N on co
Slide 21: Most Potent Coverage Across BTK Mutations Compared to Other BTK Degraders
1.4 3.4 0.8 2.5 6.6 2.0 5.1 7.1 2.0 2.8 9.4 56.3 3.7 16.2 15.3 6.9 1.6 0.3 WT C48 1S C48 1R V41 6L T47 4I L5 28 W Bexobrutideg BGB-16673 AbbVie cmpd. 1 GI50 (nM)0 20 40 60 Bexobrutideg Displays the Most Potent Coverage Across BTK Mutations Compared to Other BTK Degraders 21 Cell Killing Activity Acr
Slide 22: 600 mg Once Daily Dose Achieves Optimal Coverage of Wild Type and Mutant BTK
Once a Day 600 mg Oral Dose of Bexobrutideg Achieves Optimal Coverage of Wild Type and Mutant BTK in CLL 22 Note: Some patients have multiple BTK mutations BTK degradation in CLL patients Arithmetic Mean (SEM) of n=90 are plotted for PK concentrations; PK Datacut: 27 May 2025 Avg = average; BTK = Br
Slide 23: Bexobrutideg Is an Exquisitely Selective BTK Degrader
Bexobrutideg Is an Exquisitely Selective BTK Degrader Global Proteomics in human PBMCs at clinically relevant exposures • Global proteomics analysis reveals bexobrutideg selectively degrades BTK, displaying no off-target degradation • BGB-16673 and AbbVie cmpd. 1 exhibit off-target liabilities inclu
Slide 24: Bexobrutideg Has Best-In-Class Selectivity of BTK Over TEC
Bexdeg BGB-16673 AbbVie cmpd. 1b Acala. Zanu. Ibrutinib BTK/TEC Selectivityc,d 64x 3x 7x 25x 7x 7x 0.0 00 1 0.0 01 0.0 1 0.1 1 10 10 0 10 00 0 25 50 75 100 125 Bexobrutideg (nM) % R em ai ni ng BTK TEC 0.0 00 1 0.0 01 0.0 1 0.1 1 10 10 0 10 00 0 25 50 75 100 125 BGB-16673 (nM) % R em ai ni ng BTK TE
Slide 25: Bexobrutideg Has Best-In-Class Selectivity
• LCK humans with loss of LCK have combined immune deficiency syndrome with severely defective T cell signaling and suffer from opportunistic infections1 • CSK human genetics shows low expression is associated with hypertension; knockdown in animal models causes hypertension2 • ADK is an important m
Slide 26: Extending our leadership into I&I with potential best-in-class agents
Extending our leadership into I&I with potential best- in-class agents 26
Slide 27: Building a High-Value I&I Franchise with Best-in-Class Mechanisms
Building a High-Value I&I Franchise with Best-in-Class Mechanisms for Validated Targets 27 Program Target Modality Therapeutic area Discovery IND-Enabling Phase 1A Phase 1B Phase 2/3 Bexobrutideg (NX-5948) BTK Degrader Autoimmune cytopenia in CLL patients NX-0479 / GS-6791 IRAK4 Degrader Rheumatoid
Slide 28: NX-3911: A Potential Best-in-Class STAT6 Degrader in Collaboration with Sanofi
NX-3911: A Potential Best-in-Class STAT6 Degrader in Collaboration with Sanofi that Achieves Complete STAT6 Pathway Blockade 28 The STAT6 Transcription Factor: Acts as a key regulator of the JAK/STAT signaling pathway selectively downstream of the inflammatory cytokines IL-4 and IL-13 Drives Th2
Slide 29: NX-3911 Degrades STAT6 With Picomolar Potency in Disease Relevant Cells
NX-3911 Degrades STAT6 With Picomolar Potency in Disease Relevant Cells 29 Primary Human Cell Type DC50 (nM) Human PBMCs 0.09 Human IL-4 stimulated PBMCs 0.09 Human IL-13 stimulated PBMCs 0.08 • Potent STAT6 degradation in multiple primary human disease relevant cell types: immune cells, epidermal k
Slide 30: NX-3911 Degrades STAT6 With Exquisite Selectivity
NX-3911 Degrades STAT6 With Exquisite Selectivity 30 Global Proteomics in Human PBMCs Ad ju st ed p -v al ue (- lo g1 0 sc al e) Fold change (log2 scale) • Highly selective degradation of STAT6 in human PBMCs (global proteomics assessed at 24h at 50x DC50) • No significant change observed for any ot
Slide 31: NX-3911 Has Demonstrated Activity in Models of Atopic Dermatitis and Asthma
NX-3911 Has Demonstrated Activity in Inflammatory Disease Models of Atopic Dermatitis and Asthma 31 - + + + + + + + 0 200 400 600 Ig E Le ve ls (n g/ m l) - + + + + + + + 0 2000 4000 6000 8000 Ig E Le ve ls (n g/ m l) Asthma Model Suppression of IgE production Atopic Dermatitis Model Suppression of
Slide 32: IRAK4 Degrader NX-0479/GS-6791: Potential Treatment for Rheumatoid Arthritis
IRAK4 Degrader NX-0479/GS-6791: Potential Treatment for Rheumatoid Arthritis and Other Inflammatory Diseases Source: Teng et al., ACR 2024, November 2024 .32 Phase 1 initiated by collaboration partner Gilead Sciences in Q2 2025; Nurix has a co-development and 50/50 profit share option in the United
Slide 33: NX-0479/GS-6791 Elicits Best-in-Class IRAK4 Degradation
NX-0479/GS-6791 Elicits Best-in-Class IRAK4 Degradation and Inhibition of Functional Responses in Skin Epithelial Systems TSLP: Thymic Stromal Lymphopoietin IRAK4 degradation and functional inhibition assessed at 1 µM test article concentration Source: Gilead Sciences data 33 Deeper IRAK4 degradatio
Slide 34: Driving Value with Wholly Owned and Partnered Programs
Arthur T. Sands, M.D., Ph.D. President and Chief Executive Officer Driving Value with Wholly Owned and Partnered Programs
Slide 35: Building an Oncology and Immunology Powerhouse
• Bexobrutideg has the potential to produce a pipeline of value over the course of its lifecycle • CLL, WM, NHL, and potentially I&I indications • Advancing bexobrutideg one step closer to registration and commercialization 600 mg dose selected per Project Optimus Regulatory alignment on dose wi
Slide 36: Paths to Value Creation
Forecast milestones for bexobrutideg and select I&I programs Paths to Value Creation * Nurix estimate for partnered programs using industry standard timelines based on current stage of development (not official guidance of partners).36 2025 Bexobrutideg: potential best-in- class leadership in CLL Ex
Slide 37: Q&A
Q&A CONFIDENTIAL
Slide 38: Thank you
NURIX Thank you CONFIDENTIAL
Slide 39: Appendix: First-in-Class CBL-B Inhibitor NX-1607 Phase 1a Data (ESMO 2025)
ESMO 2025 poster presentation Presented October 18, 2025 Appendix: First-in-Class CBL-B Inhibitor NX-1607: Phase 1a Data in Patients with Advanced Solid Tumors
Slide 40: CBL-B Is a Cytoplasmic E3 Ubiquitin Ligase Targeting T Cell Activation
• Inhibition of CBL-B removes an intracellular checkpoint that negatively regulates T cell activation, thereby allowing more robust T cell activation, reversal of T-cell exhaustion, and alleviation of tumor-induced immunosuppression • NX-1607 is a first-in-class oral inhibitor of CBL-B, offering a n
Slide 41: NX-1607-101 Study Design – Phase 1a/b Trial
Phase 1a monotherapy dose escalation NX-1607-101 Study Design – Phase 1a/b Trial in Adults with Advanced Solid Tumors Source: First-in-Class CBL-B Inhibitor NX-1607: Phase 1a Data in Patients with Advanced Solid Tumors, ESMO 2025 QD, once daily; BID, twice daily; ECOG PS, Eastern Cooperative Oncolog
Slide 42: Patient Disposition
Patient Disposition Source: First-in-Class CBL-B Inhibitor NX-1607: Phase 1a Data in Patients with Advanced Solid Tumors, ESMO 202542
Slide 43: Patient Demographics and Baseline Disease Characteristics
Elderly population with advanced cancer enrolled after multiple lines of prior treatment, including prior immuno-oncology therapies Patient Demographics and Baseline Disease Characteristics Source: First-in-Class CBL-B Inhibitor NX-1607: Phase 1a Data in Patients with Advanced Solid Tumors, ESMO 202
Slide 44: Dose-Dependent Pharmacokinetics and pHS1 Pharmacodynamics
NX-1607 demonstrates dose-dependent pharmacokinetics; NX-1607 increases the percentage of pHS1-positive CD8-T cells from baseline across dose cohorts Dose-Dependent Pharmacokinetics with Associated Increases in Pharmacodynamics of the CBL-B Proximal Biomarker pHS1 Source: First-in-Class CBL-B Inhibi
Slide 45: Dose-Responsive Peripheral Immune Activation: CXCL10 and CCL4
NX-1607 led to an increase in the peripheral chemokines, CXCL10 and CCL4, at Cycle 2 Day 15, suggesting the upregulation of pro-inflammatory signaling and corresponding immune cell recruitment NX-1607 Demonstrates Dose-Responsive Peripheral Immune Activation via Increases in Distal Biomarkers: Chemo
Slide 46: Gene Expression in PBMCs Demonstrates Dose-Responsive Immune Pathway Modulation
Gene Expression in PBMCs Demonstrates Dose-Responsive Modulation of Immune Pathway Activation by NX-1607 Source: First-in-Class CBL-B Inhibitor NX-1607: Phase 1a Data in Patients with Advanced Solid Tumors, ESMO 202546 • Transcriptomic profiling demonstrated dose-responsive enrichment of key immune
Slide 47: NX-1607 Safety Profile Comparable to Approved Immuno-oncology Agents
Most adverse events were ≤Grade 2 in severity; Active doses of ≥30mg are tolerable. NX-1607 Has a Safety Profile Comparable to Approved Immuno-oncology Agents in Early Development Source: First-in-Class CBL-B Inhibitor NX-1607: Phase 1a Data in Patients with Advanced Solid Tumors, ESMO 202547
Slide 48: Duration of Treatment and Response by Tumor Type
Duration of Treatment and Response by Tumor Type in Patients Receiving Doses ≥30mg BID Source: First-in-Class CBL-B Inhibitor NX-1607: Phase 1a Data in Patients with Advanced Solid Tumors, ESMO 202548
Slide 49: NX-1607 Treatment Demonstrates Preliminary Signals of Clinical Benefit
NX-1607 Treatment Demonstrates Preliminary Signals of Clinical Benefit 49 aDays (months) of clinical benefit calculated from C1D1 until clinical/radiological progression, adverse event or withdrew consent bPatients are ongoing as of the data cut cBone-only disease and thus no corresponding tumor vol
Slide 50: Clinical Activity in Patients with CRPC: PSA Reduction
BID dosing shows promising and meaningful reductions in PSA in patients with CRPC Clinical Activity in Patients with CRPC: ≥50% reduction of PSA Source: First-in-Class CBL-B Inhibitor NX-1607: Phase 1a Data in Patients with Advanced Solid Tumors, ESMO 2025 CRPC, Castration-Resistant Prostate Cancer;
Slide 51: Case Study 1: Patient with MSS Colorectal Cancer
Case Study 1: Patient with MSS Colorectal Cancer MSS, micro-satellite stable Source: First-in-Class CBL-B Inhibitor NX-1607: Phase 1a Data in Patients with Advanced Solid Tumors, ESMO 202551
Slide 52: Case Study 2: Patient with Castration-Resistant Prostate Cancer
Case Study 2: Patient with Castration-Resistant Prostate Cancer (CRPC) Source: First-in-Class CBL-B Inhibitor NX-1607: Phase 1a Data in Patients with Advanced Solid Tumors, ESMO 202552
Slide 53: NX-1607 Is a First-in-Class Oral CBL-B Inhibitor: Conclusions
• NX-1607 is a first-in-class oral CBL-B inhibitor demonstrating a novel immune checkpoint mechanism distinct from PD-1/PD-L1 • NX-1607 is tolerable at pharmacologically active doses • Oral dosing of NX-1607 demonstrated dose-dependent exposure, increases in proximal and distal biomarkers, evidence
Nurix Therapeutics — Investor Presentation (October 2025) on 6ix