Nurix Therapeutics, Inc. · NASDAQ:NRIX
Nurix Therapeutics — TPD Conference 2020
20 slides from Nurix Therapeutics's conference presentation, Oct 14, 2020
Slide 1: Nurix Therapeutics: Blazing a New Path in Medicine
Nurix Therapeutics Blazing a New Path in Medicine Targeted Protein Modulation: Harnessing or Inhibiting E3 Ligases to Decrease or Increase Protein Levels TPD Conference 2020 Exhibit 99.1
Slide 2: Important Notice and Disclaimers
Important Notice and Disclaimers This presentation contains forward-looking statements and information relating to Nurix Therapeutics, Inc. (the “Company,” “we," "us" or "our"). Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based on o
Slide 3: Nurix: A Targeted Protein Modulation Company
©Nurix Therapeutics. All rights reserved. Targeting E3 ligases to develop small molecule targeted protein modulation drug candidates that can increase or decrease protein levels Four wholly-owned oncology and immunology drug candidates with first clinical trial expected to commence in H1 2021 Applyi
Slide 4: DELigase Platform Enables Two Complementary Protein Modulation Approaches
DELigaseTM: Platform Enables Two Complementary Protein Modulation Approaches for Drug Discovery ©Nurix Therapeutics. All rights reserved. Protein Modulation Platform Drug Development BB2 BB3 BB1 Proprietary DNA-Encoded Libraries, >109 compounds Expanded universe of E3 ligases, >30 ligases currently
Slide 5: DELigase Identifies a Spectrum of Binders Across the Ligase Surface
DELigaseTM Identifies a Spectrum of Binders Across the Ligase Surface ©Nurix Therapeutics. All rights reserved.
Slide 6: Ligase Inhibitors Can Increase Levels of Specific Substrate Proteins
Ligase Inhibitors Can Increase Levels of Specific Substrate Proteins ©Nurix Therapeutics. All rights reserved. Substrate Protein E3 Ligase Ubiquitin Natural E3 Ligase-Mediated Proteasomal Degradation Catalytic ubiquitination E3 Ligase Ligase Inhibitors Substrate Protein Substrate Protein Proteasomal
Slide 7: Wholly-Owned Targeted Protein Modulation Drug Pipeline
Drug Candidate Target / Delivery Therapeutic Area Lead Optimization Preclinical Phase 1 Phase 2 Phase 3 Protein Degradation Chimeric Targeting Molecule (CTM) Portfolio NX-2127 BTK + IMiD activity Oral B-cell Malignancies NX-5948 BTK Oral B-cell Malignancies And GVHD Ligase Inhibition Portfolio NX-16
Slide 8: CBL-B: A Modulator of T Cell Activation for Tumor Immunotherapy
CBL-B: A Modulator of T Cell Activation for Tumor Immunotherapy CBL-B is an E3 ligase that regulates the immune system by specifically degrading proteins involved in shutting off T-cell signaling Blocking CBL-B removes a brake on the immune system CBL-B function is supported by mouse and human genet
Slide 9: CBL-B Knockout Validation: Enhanced IL-2 Secretion, Tumor Growth Inhibition, and Survival
CBL-B Knockout Validation: Enhanced IL-2 Secretion, Tumor Growth Inhibition, and Survival ©Nurix Therapeutics. All rights reserved.
Slide 10: Nurix CBL-B Inhibitors Elevate IL-2 Levels ex vivo in Human Donor T Cells
Nurix CBL-B Inhibitors Elevate IL-2 Levels ex vivo in Human Donor T Cells ©Nurix Therapeutics. All rights reserved. Several fold increase in IL-2 production corresponds with increasing biochemical activity of CBL-B inhibitors CBL inhibition results in increased T cell activation in the absence of co
Slide 11: Once Daily Oral Dosing of NX-1607 Recapitulates Anti-Tumor Effects of CBL-B Knock-in
Once Daily Oral Dosing of NX-1607 Recapitulates Anti-Tumor Effects of CBL-B, Ligase Inactive, Knock-in Mouse Model ©Nurix Therapeutics. All rights reserved. CBL-B ligase-dead, knock-in (KI) model Oral daily dosing of NX-1607 Two Way ANOVA of treatment group vs vehicle control Average tumor volumes f
Slide 12: NX-1607 and Anti-PD-1 Synergize to Improve Anti-Tumor Effects and Survival
NX-1607 and Anti-PD-1 Synergize to Improve Anti-Tumor Effects and Survival of Tumor-bearing Mice ©Nurix Therapeutics. All rights reserved. **** ** * Log-rank (Mantel-Cox) test of vehicle vs treatment Combination of NX-1607 and anti-PD-1 treatment significantly improves anti-tumor response and surviv
Slide 13: NX-1607 Induces Long Term Survival in Metastatic Breast Cancer Model
NX-1607 Induces Long Term Survival in Metastatic, Triple Negative, Breast Cancer Model ©Nurix Therapeutics. All rights reserved. Triple negative breast carcinoma cells metastasize from subcutaneous space to distant sites Survival in Metastatic Breast Cancer Model Day 15: Surgical removal of primary
Slide 14: Pharmacologic Control of Adoptive Cell Therapy with Targeted Protein Modulation
Introducing Pharmacologic Control of Adoptive Cell Therapy with Targeted Protein Modulation ©Nurix Therapeutics. All rights reserved. Adoptive Cell Therapy Nurix Adoptive Cell Therapy Program Drug-Enhanced Tumor Infiltrating Lymphocytes Drug-Enhanced Chimeric Antigen Receptor T Cell Therapy Small mo
Slide 15: NX-0255 ex vivo Treatment Provides Robust Anti-Tumor Activity in Mouse Model
NX-0255 ex vivo Treatment Provides Robust Anti-Tumor Activity in Mouse Model ©Nurix Therapeutics. All rights reserved. Improvement in Conditional Survival in Mouse ACT Tumor Model Reduction in Tumor Growth in Mouse ACT Tumor Model CD8+ cells exposed to NX-0255 alone ex vivo resulted in superior cond
Slide 16: Oral NX-1607 Augments Anti-Tumor Activity with ex vivo NX-0255
Oral NX-1607 Augments Anti-Tumor Activity Observed with ex vivo NX-0255 Combination in ACT Mouse Model ©Nurix Therapeutics. All rights reserved. Reduction in Tumor Growth in Mouse ACT Tumor Model Improvement in Conditional Survival in Mouse ACT Tumor Model Oral NX-1607 treatment once daily further e
Slide 17: CBL-B Inhibitors to Enhance Adoptive Cell Therapy: DeTIL and DeCART
CBL-B Inhibitors to Enhance Adoptive Cell Therapy: DeTILTM and DeCARTTM ©Nurix Therapeutics. All rights reserved. Oral CBL-B inhibition For co-administration to enhance engraftment to improve anti-tumor activity or to treat relapse Ex-vivo CBL-B inhibition For enhanced isolation of T cells for TIL o
Slide 18: Matching the Right Business Strategy with Each NxACT Opportunity
Matching the Right Business Strategy with Each NxACT Opportunity ©Nurix Therapeutics. All rights reserved. Drug-Enhanced Tumor Infiltrating Lymphocytes Drug-Enhanced Chimeric Antigen Receptor T Cell Therapy TIL research and development being built out in Pittsburgh and Philadelphia by industry leadi
Slide 19: Summary
Summary DELigase has produced highly potent hits to ligases Specific ligase inhibitors can result in pathway-specific changes in ubiquitination status associated with potent biologic effects CBL-B inhibitors activate T cells and demonstrate single agent and combination anti-tumor activity in syngene
Slide 20: Thank you
Thank you Nurix Therapeutics