Nurix Therapeutics, Inc. · NASDAQ:NRIX
Nurix Therapeutics — Investor Presentation (January 2022)
30 slides from Nurix Therapeutics's investor presentation, Jan 10, 2022
Slide 1: Blazing a New Path in Medicine
Nurix Therapeutics Blazing a New Path in Medicine Investor Presentation January 2022 Exhibit 99.1
Slide 2: Important Notice and Disclaimers
Important Notice and Disclaimers This presentation contains information relating to Nurix Therapeutics, Inc. (the “Company,” “we," "us" or "our") and forward-looking statements within the meaning of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking
Slide 3: Leading the Field of Targeted Protein Modulation
©Nurix Therapeutics. All rights reserved. Leading the Field of Targeted Protein Modulation Industry leading targeted protein modulation platform over 5 billion DEL compounds 15 targeted protein degradation drug discovery programs advancing from DELigase platform Regulatory clearance to initiate four
Slide 4: Nurix Delivered on Key Milestones in 2021
Initiate Phase 1 trial IND accepted by FDA Enrollment anticipated in H1 2022 Complete engineering manufacturing runs Define differentiated profile Crosses blood brain barrier in animals Active in autoimmune animal models Nurix Delivered on Key Milestones in 2021, a Year of Significant Execution ©Nur
Slide 5: Advancing Four Wholly Owned Clinical Programs with a Deep Pipeline
©Nurix Therapeutics. All rights reserved. Advancing Four Wholly Owned Clinical Programs with a Deep Pipeline of Proprietary and Partnered Novel Targets Drug Program Target / Delivery Therapeutic Area Discovery IND enabling Phase 1 Phase 2 Phase 3 NX-2127 Degrader BTK + IMiD activity Oral B-cell Mali
Slide 6: Nurix's DELigase Platform: Leading the Industry in DNA-Encoded Libraries
©Nurix Therapeutics. All rights reserved. Nurix’s DELigase Platform: Leading the Industry in DNA-Encoded Libraries for Targeted Protein Modulation DELigase Protein Modulation Platform BB2 BB3 BB1 Proprietary DNA-Encoded Libraries, > 5x109 compounds >30 E3 ligases currently in discovery Chimeric Targ
Slide 7: DELigase Enables Efficient Chimeric Targeting Molecule Discovery and Design
DELigase® Enables Efficient Chimeric Targeting Molecule Discovery and Design ©Nurix Therapeutics. All rights reserved. CTM DNA Barcode Binders from DEL are joined via a linker to construct CTMs CTM recruits E3 ligase to target protein, triggering ubiquitin transfer and degradation Target E3 Ligase T
Slide 8: Nurix's BTK Degrader Portfolio: A Differentiated Approach to B-Cell Malignancies
Nurix’s BTK Degrader Portfolio: A Differentiated Approach to B-Cell Malignancies BTK is standard of care target however mutational escape represents a major unmet need BTK inhibitors are approved for CLL/SLL, mantle cell lymphoma, Waldenstrom's macroglobulinemia, marginal zone lymphoma, with estimat
Slide 9: NX-2127 Degrades Both BTK and IMiD Neosubstrate Aiolos
NX-2127 Degrades Both BTK and IMiD Neosubstrate Aiolos NX-2127 shows potent BTK degradation in TMD8 cells (human DLBCL cell line) NX-2127 degradation of Aiolos in human T cells occurs at a similar potency to lenalidomide and pomalidomide ©Nurix Therapeutics. All rights reserved. BTK Degradation in T
Slide 10: NX-2127 Potently Inhibits Growth of Ibrutinib-Resistant Tumor Cell Lines
NX-2127 Potently Inhibits Growth of Ibrutinib-Resistant Tumor Cell Lines NX-2127 retains potent growth inhibition relative to BTK inhibitors in a tumor cell line carrying the C481S mutation Degradation of BTK with NX-2127 may offer a therapeutic option for patients who develop resistance to BTK inhi
Slide 11: Advantage of IMiD Activity Plus BTK Degradation in REC-1 Cells
The next generation non-covalent BTK inhibitor, pirtobrutinib, has an activity curve similar to other BTK inhibitors NX-2127 shows similar potency and greater depth of cell killing compared to pirtobrutinib Compounds active against BTK reduce cell viability at low doses, but this effect plateaus IMi
Slide 12: Increasing BTK Degradation Correlates with Tumor Growth Inhibition
TMD8 Tumors Increasing BTK Degradation Correlates with Significant Tumor Growth Inhibition N/A: Not applicable; TGI: tumor growth inhibition. Treatment Oral gavage dose (mg/kg) % BTK degradation in circulating B cells % BTK degradation in TMD8 tumor tissue % TGI vs Vehicle (Day 24) P value vs Vehicl
Slide 13: NX-2127-001: Phase 1 First-in-Human Clinical Trial Design
NX-2127-001: Phase 1 First-in-Human Clinical Trial Design Two-Part Phase 1 Monotherapy Trial of NX-2127 in Relapsed or Refractory B-Cell Malignancies Dose Escalation Dose escalation Status* Complete Potential Dose Expansion CLL with BTK C481 mutation (n≈20) CLL unselected (n≈20) MCL, MZL, WM (n≈20)
Slide 14: Robust BTK Degradation Observed in All Patients Dosed
Robust BTK Degradation Observed in All Patients Dosed Regardless of Baseline BTK Protein Levels MFI: geometric mean fluorescence intensity in circulating CD19+ B cells. Oral daily treatment of NX-2127 induced a rapid and significant decrease in BTK levels that was sustained throughout dosing Patient
Slide 15: BTK Degradation Table of Enrolled Patients
BTK Degradation Table of Enrolled Patients Dose Patient % BTK Degraded Baseline Day 2 Day 8 Day 15 Day 22 Day 29 Average Steady State* Day 56 100 mg Patient 1 (CLL) 0 62.8 76.9 78.0 85.5 82.0 81.8 81.4 200 mg Patient 2 (CLL) 0 75.1 90.5 96.1 95.4 96.1 95.9 96.0 Patient 3 (MCL) 0 74.0 92.7 94.6 95.4
Slide 16: Clinical Response Observed in Patient
Clinical Response Observed in Patient 1 ©Nurix Therapeutics. All rights reserved. Patient History: 78-year-old male with stage IV CLL Prior Treatments: 1. Rituximab, 2015 2. Ibrutinib, 2015-2021 Disease at Study Entry: Bone Marrow Involvement: 85.4% Spleen: Enlarged (15.7 cm) Nodal Lesions: Several,
Slide 17: NX-5948 is a Differentiated BTK Degrader
NX-5948 is a Differentiated BTK Degrader Being Developed for CLL/NHL and Autoimmune Diseases ©Nurix Therapeutics. All rights reserved. Differentiated profile NX-5948 retains potent activity against both wild type and mutant BTK NX-5948 spares IMiD activity, unlike NX-2127 NX-5948 crosses the blood b
Slide 18: NX-5948-301: Phase 1 First-in-Human Clinical Trial Design
NX-5948-301: Phase 1 First-in-Human Clinical Trial Design Two-Part Phase 1 Monotherapy Trial of NX-5948 in Relapsed or Refractory B-Cell Malignancies Dose Escalation Dose escalation Potential Dose Expansion CLL with BTK C481 mutation CLL unselected DLBCL or MCL FL, MZL, or WM Primary CNS lymphoma Ob
Slide 19: CBL-B: A Modulator of T Cell Activation and Novel Immuno-oncology Target
CBL-B: A Modulator of T Cell Activation and a Novel Target for Immuno-oncology CBL-B is an E3 ligase that regulates the immune system by specifically ubiquitinating proteins involved in signaling through the T cell antigen receptor Blocking CBL-B removes a brake on the immune system CBL-B function i
Slide 20: NX-1607 Elevates Cytokines Including IL-2 in Human Donor T Cells
CBL-B Inhibitor NX-1607 Elevates Cytokines Including IL-2 in Human Donor T Cells ©Nurix Therapeutics. All rights reserved. NX-1607 increases stimulation-dependent production of key activation cytokines NX-1607 has no impact in the absence of T cell stimulation Oral NX-1607 is expected to produce key
Slide 21: Single-Agent NX-1607 Induces Long Term Survival in Breast Cancer Model
Single-Agent NX-1607 Induces Long Term Survival in Metastatic, Triple Negative, Breast Cancer Model ©Nurix Therapeutics. All rights reserved. 4T1 breast carcinoma cells metastasize from subcutaneous space to distant sites Survival in Metastatic Breast Cancer Model Day 15: Surgical removal of primary
Slide 22: NX-1607 and Anti-PD-1 Synergize to Enhance Anti-Tumor Effects
Combination of NX-1607 and Anti-PD-1 Synergize to Enhance 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 resp
Slide 23: NX-1607-101: Phase 1 First-in-Human Clinical Trial Design
NX-1607-101: Phase 1 First-in-Human Clinical Trial Design Two-Part Phase 1 Monotherapy Trial of NX-1607 in Relapsed or Refractory Tumors Dose Escalation Dose escalation Potential Dose Expansion Melanoma Squamous Cell Carcinoma of the Head and Neck (HNSCC) Platinum Resistant Epithelial Ovarian Cancer
Slide 24: Drug Enhanced Tumor Infiltrating Lymphocytes (DeTIL-0255)
Drug Enhanced Tumor Infiltrating Lymphocytes (DeTIL-0255) ©Nurix Therapeutics. All rights reserved. DeTIL-0255 is created by ex vivo CBL-B inhibition with small-molecule NX-0255, producing a TIL cell therapy product with enhanced characteristics that overcomes the major limitations of current TIL th
Slide 25: NX-0255 ex vivo Treatment Provides Robust Anti-Tumor Activity
NX-0255 ex vivo Treatment Provides Robust Anti-Tumor Activity in Mouse Model of Adoptive T Cell Therapy ©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 viv
Slide 26: 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 27: DeTIL-0255-201: Phase 1 First-in-Human Clinical Trial Design
DeTIL-0255-201: Phase 1 First-in-Human Clinical Trial Design Two-Part Phase 1 Monotherapy Trial of DeTIL-0255 in Relapsed or Refractory Gynecological Cancers Safety Run in (3-6 patients) Cohort Expansion Platinum Resistant Epithelial Ovarian Cancer (~ 15 patients) Recurrent, Metastatic or Persistent
Slide 28: Advancing Our Pipelines with Financial Strength
Advancing Our Proprietary and Partnered Pipelines with Financial Strength ©Nurix Therapeutics. All rights reserved. Financial Highlights $465 million in cash as of August 31, 2021 $518 million raised in equity financings in 2020-2021 $276 million to date from partnership upfront payments $19.5 milli
Slide 29: Advancing Our Pipeline to Multiple Clinical Milestones in 2022
Advancing Our Pipeline to Multiple Clinical Milestones in 2022 NX-2127 Initiate Phase 1b trial in mid-2022 Present additional Phase 1a clinical results in H2 2022 NX-5948 Dose first patient in Phase 1a trial in H1 2022 Establish Phase 1a PK/PD in H2 2022 ©Nurix Therapeutics. All rights reserved. NX-
Slide 30: Thank you
Thank you Nurix Therapeutics
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