Nurix Therapeutics, Inc. · NASDAQ:NRIX

Nurix Therapeutics — Technical Presentation (April 2026)

21 slides from Nurix Therapeutics's technical presentation, April 2026

  1. Slide 1: Discovery and Characterization of CBL-B Intramolecular Glue Inhibitors

    Discovery and Characterization of CBL-B Intramolecular Glue Inhibitors That Increase T Cell Activation and Suppress Tumor Growth Frederick Cohen, Ph.D. Nurix Therapeutics, Inc., Brisbane, CA

  2. Slide 2: Disclosure Information

    Disclosure Information Frederick Cohen I have the following relevant financial relationships to disclose: Employee of: Nurix Therapeutics, Inc. Stockholder in: Nurix Therapeutics, Inc. I have no other financial relationships to disclose. DO NOT POST DO NOT POST

  3. Slide 3: Disclosure Information

    Disclosure Information 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,” “beli

  4. Slide 4: CBL-B is a Master Modulator of Immune Cell Activation

    CBL-B is a Master Modulator of Immune Cell Activation ▪ CBL-B is an E3 ubiquitin ligase highly expressed in cells of the immune system ▪ CBL-B regulates T, B, and NK cell activation ▪ Blocking CBL-B removes a brake on the immune system ▪ cbl-b deficient mice demonstrate robust T cell and NK cell-med

  5. Slide 5: Inactivation of CBL-B Leads to Enhanced T Cell Activation

    Inactivation of CBL-B Leads to Enhanced T Cell Activation IL-2 secretion in knock-out (KO) and Ligase-inactive cbl-b knock-in (KI) mice inhibit ligase inactive T cells ex vivo tumor growth (TC-1 syngeneic model) Het Inactive ligase mut (C373A) Ligase KO Ligase-dead or KO exhibit similar enhancement

  6. Slide 6: CBL-B is Regulated Through Conformational Change and Phosphorylation

    CBL-B is Regulated Through Conformational Change and Phosphorylation CLOSED/INACTIVE OPEN/ACTIVE LHR TKB TKB RING LHR Tyr RING P Tyr E2~Ub E2~Ub DO NOT POST DO NOT POST

  7. Slide 7: Mechanism-Agnostic Screening Assays Guided by CBL-B Biology

    Mechanism-Agnostic Screening Assays Guided by CBL-B Biology Phospho-CBL-B Assay E2-Ub Binding Assay CBL-B CLOSED pY-CBL-B OPEN CBL-B CLOSED pY-CBL-B OPEN LHR TKB Src TKB RING ATP LHR TKB Src TKB RING ATP RING ZAP70 LHR Tyr peptide RING ZAP70 LHR PO4 Tyr Tyr peptide Streptavidin- Streptavidin- UB-Bod

  8. Slide 8: HTS and Confirmation Affords a Singleton Hit

    HTS and Confirmation Affords a Singleton Hit HTS Deck 250,000 Single Point >20% CBL-B inhibition Peptide phosphorylation (% change) HTS Hits 1113 HTS hits <20% kinase inhibition Manually Selected 104 Properties, diversity Available from Powder 90 Dose-response NRX-1 Quantified by SPR 15 Sensorgram s

  9. Slide 9: HTS and Confirmation Affords a Singleton Hit

    HTS and Confirmation Affords a Singleton Hit % change from DMSO CBL-B phosphorylation SRC Peptide phosphorylation % change from DMSO 0 0 -25 IC50 = 26 M -25 -50 -50 -75 -75 -100 -100 10 -3 10 -2 10 -1 10 0 10 1 10 2 10 3 10 -3 10 -2 10 -1 10 0 10 1 10 2 10 3 [Compound] μM [Compound] μM UbcH5b~Ub bi

  10. Slide 10: NRX-3 is a Specific Inhibitor of CBL-B

    NRX-3 is a Specific Inhibitor of CBL-B CBL-B phosphorylation SPR binding to CBL-B NRX-1 HTS Screening hit 10 NRX-2 Response (RU) NRX-3 IC 50 = 34 M 5 Chiral SFC NRX-2 0 0 30 60 90 Time (s) NRX-2 UbcH5~Ub binding 10 NRX-3 KD = 25 M Response (RU) NRX-3 5 Resolved Screening hit NRX-3 IC 50 =3 20 M m

  11. Slide 11: Crystal Structure Confirms Binding Site of NRX-3

    Crystal Structure Confirms Binding Site of NRX-3 Y363 DO NOT POST DO NOT POST

  12. Slide 12: NRX-3 Acts as an Intra-Molecular Glue Inhibitor of CBL-B

    NRX-3 Acts as an Intra-Molecular Glue Inhibitor of CBL-B DO NOT POST DO NOT POST

  13. Slide 13: Early SAR: Focus on Affinity and Properties

    Early SAR: Focus on Affinity and Properties NRX-3 NRX-4 NRX-5 NRX-6 NRX-8766 E2-Ub: IC 50 (M) ~20 0.23 0.092 0.088 0.021 LipE (pIC50-cLogP) 1.7 2.8 2.3 3.4 6.4 Cellular Substrate Ub IC 50 7 3 1.7 0.79 (M) DO NOT POST DO NOT POST

  14. Slide 14: Pharmacologic Inhibition of CBL-B Recapitulates Anti-Tumor Effects of Genetic Model

    Pharmacologic Inhibition of CBL-B Recapitulates Anti- Tumor Effects of Genetic Model of Ligase Inhibition Ligase-inactive cbl-b knock-in mice inhibit Pharmacologic Inhibition of CBL-B inhibits tumor growth in the TC-1 syngeneic model tumor growth in the CT26 Syngeneic Model 2500 Vehicle Tumor volume

  15. Slide 15: Optimization Leads to NX-1607

    Optimization Leads to NX-1607 HTS hit HTS hit, single enantiomer 2017 Biochemical potency (uM) 2018 NRX-3, screening hit 2019 IC50 = ~20 M NX-1607 LipE KD = 0.4 nM DO NOT POST DO NOT POST

  16. Slide 16: NX-1607 Increases IL-2 and IFN-g Secretion in Response to TCR Stimulation

    NX-1607 Increases IL-2 and IFN-g Secretion in Response to TCR Stimulation DO NOT POST DO NOT POST

  17. Slide 17: Single-Agent NX-1607 Induces Anti-tumor Response in Multiple Models

    Single-Agent NX-1607 Induces Anti-tumor Response in Multiple Models Colorectal Triple-Negative Breast B Cell Lymphoma (CT26) (4T1) (A20) Shaded area indicates dosing period: NX-1607 (30 mg/kg, PO daily) DO NOT POST DO NOT POST

  18. Slide 18: NX-1607 and Anti-PD-1 Synergize to Enhance Survival in Multiple Models

    NX-1607 and Anti-PD-1 Synergize to Enhance Survival in Multiple Models Colorectal Colorectal Triple-Negative Breast (CT26) (MC38) (4T1) Long-Term Survival Long-Term Survival 100 Day 28 4T1 Lung Metastases % Conditional Survival 100 p<0.01 % Conditional Survival # Metastatic Colonies 15000 p<0.01 100

  19. Slide 19: NX-1607 Displays Favorable Preclinical Profile

    NX-1607 Displays Favorable Preclinical Profile NX-1607 Properties Parameter Value NHP 10000 [NX-1607] mean (ng/mL) mw 537.6 amu Dog 1000 Rat pKa/LogD 7.4 8.3/3.5 100 Mouse kon= 2.2 x 105 M-1s-1 Solubility (PBS, 10 230 uM koff = 8.6 x 10-5 s-1 pH=7.4) 1 KD = 0.4 nM KD CBL-B (nM) spr 0.4 nM T1/2 = 2.2

  20. Slide 20: NX-1607 Demonstrates Dose-Dependent PK and Modulation of Biomarker pHS1 in Patients

    NX-1607 Demonstrates Dose-Dependent PK and Modulation of Biomarker pHS1 in Patients Steady state pharmacokinetics Pharmacodynamic activity of pHS1 in CD8 T cells 200 AUC0-4h of pHS1+CD8 cells (h*%) 150 100 50 0 2) ) ) =6 =8 =6 ) =4 ) 0) 0) =1 (n (n (n (n =1 =1 (n D D D (n (n D D Q g Q g Q BI BI BI D

  21. Slide 21: Summary

    Summary ▪ Deep understanding of CBL-B regulation allowed design of mechanism-agnostic screening assays ▪ HTS and careful follow-up afforded a singleton hit ▪ This series functions as an intra-molecular glue, stabilizing the closed, inactive state of CBL-B ▪ Optimization resulted in NX-1607, a potent

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