Nurix Therapeutics, Inc. · NASDAQ:NRIX
Nurix Therapeutics — 4th Annual Targeted Protein Degradation (TPD) Summit (October 2021)
24 slides from Nurix Therapeutics's conference presentation, Oct 27, 2021
Slide 1: Blazing a New Path in Medicine: First Demonstration of TPD of BTK
Nurix Therapeutics Blazing a New Path in Medicine First Demonstration of Targeted Protein Degradation of BTK in Hematologic Malignancies: Initial NX-2127 Phase 1a PK/PD Data 4th Annual Targeted Protein Degradation (TPD) Summit October 27, 2021 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: Arthur T. Sands, M.D., Ph.D., Chief Executive Officer
Arthur T. Sands, M.D., Ph.D. Chief Executive Officer 4th Annual Targeted Protein Degradation (TPD) Summit October 27, 2021
Slide 4: Presentation Outline
Presentation Outline Outline of key questions we plan to address: What is the status of our protein modulation pipeline? What levels of BTK degradation are associated with anti-tumor effects in animal models? What are the initial PK/PD findings from the Phase 1a study of NX-2127 in patients with rel
Slide 5: Nurix's Wholly-Owned Targeted Protein Modulation Pipeline
©Nurix Therapeutics. All rights reserved. Nurix’s Wholly-Owned Targeted Protein Modulation Pipeline: Both Degradation and Ligase Inhibition Programs Currently Enrolling Drug Candidate Target / Delivery Therapeutic Area Discovery Lead Optimization Preclinical Phase 1 Phase 2 Phase 3 Protein Degradati
Slide 6: 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 7: 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 sales o
Slide 8: 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 9: 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 10: TMD8 Tumors: 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 11: BTK Degradation with Once Daily Oral Dosing of NX-2127 in Non-Human Primates
BTK Degradation with Once Daily Oral Dosing of NX-2127 in Non-Human Primates All dose levels achieve BTK degradation consistent with anti-tumor effects in mouse model At steady state once daily, oral dosing of NX-2127 maintains suppression of BTK protein levels throughout the dosing period Day 19 Da
Slide 12: Robert J. Brown, M.D., SVP, Clinical Development
Robert J. Brown, M.D. SVP, Clinical Development 4th Annual Targeted Protein Degradation (TPD) Summit October 27, 2021
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 Dose Expansion CLL with BTK C481 mutation (n≈20) CLL unselected (n≈20) MCL, MZL, WM (n≈20) FL (n≈20) D
Slide 14: Study Disposition: Five of Six Patients Remain on Study
Study Disposition: Five of Six Relapsed/Refractory Patients Enrolled Remain on Study with NX-2127 Data as of October 18, 2021 Time on study calculated as time from dosing start date to data extraction date NX-2127 Dose Patient Disease Type No. Prior Lines Prior BTK-Targeted Therapy 100 mg 1 CLL 2 Ib
Slide 15: Daily Oral Dosing Achieves Steady State NX-2127 Levels by Day 8
Daily Oral Dosing Achieves Steady State NX-2127 Levels by Day 8 Oral daily doses of NX-2127 achieves steady state concentrations by Day 8 Oral daily dosing of NX-2127 demonstrates plasma exposure similar that observed in non-human primates ©Nurix Therapeutics. All rights reserved.
Slide 16: 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. Patients have varying levels of BTK in B cells at the start of treatment Oral daily treatment of NX-2127 induced a rapid and signif
Slide 17: Greater Than 90% BTK Degradation at Second Dose Level (200 mg)
Greater Than 90% BTK Degradation Achieved at Steady State at Second Dose Level (200 mg once daily) Cohort 1 patient with >80% BTK degradation at steady state Cohort 2 average >90% BTK degradation at steady state BTK degradation in patients was consistent with results from mouse and primate models BT
Slide 18: 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 19: No Dose Limiting Toxicities Observed in the First Two Cohorts
No Dose Limiting Toxicities Observed in the First Two Cohorts Preferred Term Dose Level (mg) Grade Relatedness Intervention Disposition Neutropenia 100 3 Yes None Resolved Neutropenia 200 3 Yes Yes Resolved Hypertension 200 3 Yes No Resolved Dyspnea 200 3 No No Resolved Pneumonia 200 3 No Yes Ongoin
Slide 20: Case Study: Patient in Cohort 1
Case Study: Patient in Cohort 1 Patient History: 78 year-old male with stage IV CLL Date of Initial Diagnosis: March 2012 Prior Treatments: 1. Rituximab (with solumedrol), 2015 2. Ibrutinib, 2015-2021 Disease at Study Entry: Bone Marrow Involvement: 85.4% Spleen: Enlarged (15.7 cm) Nodal Lesions: Se
Slide 21: Clinical Response Observed in Patient 1
Clinical Response Observed in Patient 1 ª Spleen % change is the percent change to a reference “normal” of 13 cm. b Response for this patient as per International working group on chronic lymphocytic leukemia (iwCLL) c Listed as partial remission in database. DLT: dose limiting toxicity; SAE: seriou
Slide 22: Preliminary Findings: Robust Degradation of BTK by NX-2127
Preliminary Findings: Robust Degradation of BTK by NX-2127 in All Patients Dosed NX-2127 is well-tolerated to date with no dose-limiting toxicities Safety profile at this early stage is manageable and consistent with mechanisms of action 5 of 6 patients remain on study Dose escalation has advanced t
Slide 23: Conclusions
Conclusions Nurix protein modulation pipeline now has two programs in clinical development: NX-2127 (TPD) and NX-1607 (ligase inhibition) with two more programs advancing Robust BTK degradation demonstrated by NX-2127 in patients validates Nurix’s BTK portfolio approach in targeted protein degradati
Slide 24: Questions and Answers
0 n U rixX Questions and Answers
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