Nurix Therapeutics, Inc. · NASDAQ:NRIX
Nurix Therapeutics — 4th Annual Targeted Protein Degradation (TPD) Summit 2021
24 slides from Nurix Therapeutics's conference presentation, Oct 27, 2021
Slide 1: Blazing a New Path in Medicine
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
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: 1. What is the status of our protein modulation pipeline? 2. What levels of BTK degradation are associated with anti-tumor effects in animal models? 3. What are the initial PK/PD findings from the Phase 1a study of NX-2127 in patients
Slide 5: Nurix's Wholly-Owned Targeted Protein Modulation Pipeline
Nurix’s Wholly-Owned Targeted Protein Modulation Pipeline: Both Degradation and Ligase Inhibition Programs Currently Enrolling Lead Drug Candidate Target / Delivery Therapeutic Area Discovery Optimization Preclinical Phase 1 Phase 2 Phase 3 Protein Degradation Chimeric Targeting Molecule (CTM) Portf
Slide 6: DELigase Enables Efficient Chimeric Targeting Molecule Discovery and Design
DELigase® Enables Efficient Chimeric Targeting Molecule Discovery and Design 1 Billions of proprietary 2 Target proteins and 3 Binders from 4 CTM recruits E3 ligase to DNA-Encoded E3 ligases are DEL are joined target protein, triggering Library (DEL) compounds screened using DEL via a linker ubiquit
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 – BTK inhibitors are approved for CLL/SLL, mantle cell lymphoma, Waldenstrom's macroglobulinemia, marginal zone lym
Slide 8: NX-2127 Degrades Both BTK and IMiD Neosubstrate Aiolos
NX-2127 Degrades Both BTK and IMiD Neosubstrate Aiolos BTK Degradation in TMD8 Cells Aiolos Degradation in T Cells 125 NX-2127 % Aiolos Remaining 100 %BTK Remaining Lenalidomide 100 Pomalidomide 75 75 50 50 25 25 0 0 0.001 0.01 0.1 1 10 100 1000 0.001 0.01 0.1 1 10 100 1000 10000 NX-2127 (nM) Compou
Slide 9: NX-2127 Potently Inhibits Growth of Ibrutinib-Resistant Tumor Cell Lines
NX-2127 Potently Inhibits Growth of Ibrutinib-Resistant Tumor Cell Lines TMD8 BTK-C481S • NX-2127 retains potent growth 125 NX-2127 inhibition relative to BTK inhibitors in a Ibrutinib tumor cell line carrying the C481S 100 mutation %Viable 75 • Degradation of BTK with NX-2127 may 50 offer a therape
Slide 10: Increasing BTK Degradation Correlates with Significant Tumor Growth Inhibition
Increasing BTK Degradation Correlates with Significant Tumor Growth Inhibition Circulating B cells TMD8 Tumors Tumor Growth 120 120 1400 Vehicle Vehicle Vehicle Tumor volume, mm3 100 10 mpk 100 10 mpk 1200 % BTK remaining % BTK remaining 10 mpk NX-2127 (Mean ± SEM) 30 mpk 30 mpk 1000 30 mpk NX-2127
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 Day 1 Day 19 125 125 %BTK Remaining %BTK Remaining 100 100 Vehicle 75 75 1 mpk NX-2127 50 50 3 mpk NX-2127 25 10 mpk NX-2127 25 0 0 0 4 8 12 16 20 24 0 4 8 12 16 20 24 Time post dose (hrs) Time post dose (hrs) • All dose le
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 Expansion Objectives: - Assess safety and tolerability - Identify maximum tolerated dose CLL with BTK C481 mutation - Evaluate PK
Slide 14: Study Disposition: Five of Six Patients Remain on Study with NX-2127
Study Disposition: Five of Six Relapsed/Refractory Patients Enrolled Remain on Study with NX-2127 7 Patients Screened, 6 Patients enrolled No. NX-2127 Disease Prior BTK-Targeted 8 Week 16 Week Patient Prior DLT Period Disease Assessment Disease Assessment Dose Type Therapy Lines 100 mg 1 CLL 2 Ibrut
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 NX-2127 Plasma Level • Oral daily doses of NX- Concentration (ng/mL) 2127 achieves steady 100 Patient 1 (CLL) 100 mg state concentrations by Patient 2 (CLL) 200 mg Day 8 10 Patient 3 (MCL) 200 mg Patient 4 (WM) 200 mg • Oral daily dosin
Slide 16: Robust BTK Degradation Observed in All Patients Dosed
Robust BTK Degradation Observed in All Patients Dosed Regardless of Baseline BTK Protein Levels BTK Levels in Circulating B Cells 24000 Patient 1 (CLL) 100 mg • Patients have varying levels of BTK in B cells 20000 Patient 2 (CLL) 200 mg at the start of treatment Patient 3 (MCL) 200 mg 16000 BTK MFI
Slide 17: Greater Than 90% BTK Degradation Achieved at Steady State at 200 mg
Greater Than 90% BTK Degradation Achieved at Steady State at Second Dose Level (200 mg once daily) BTK Degradation • Cohort 1 patient with >80% BTK degradation at 100 Patient 1 (CLL) 100 mg Patient 2 (CLL) 200 mg % BTK Remaining steady state 75 Patient 3 (MCL) 200 mg • Cohort 2 average >90% Patient
Slide 18: BTK Degradation Table of Enrolled Patients
BTK Degradation Table of Enrolled Patients % BTK Degraded Average Dose Patient Baseline Day 2 Day 8 Day 15 Day 22 Day 29 Steady Day 56 State* 100 mg Patient 1 (CLL) 0 62.8 76.9 78.0 85.5 82.0 81.8 81.4 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 92.3 94
Slide 19: No Dose Limiting Toxicities Observed in the First Two Cohorts
No Dose Limiting Toxicities Observed in the First Two Cohorts • No deaths • No related serious adverse events • NX-2127 appears to be well tolerated at All©Nurix Grade 3 AllorrightsGreater Therapeutics. reserved. Adverse Events this early stage with a Preferred Term Dose Level Grade Relatedness Inte
Slide 20: Case Study: Patient in Cohort 1
Case Study: Patient in Cohort 1 Up to 68% of Leukemia Cells Patient History: with BTK Mutations 78 year-old male with stage IV CLL Date of Initial Diagnosis: March 2012 Prior Treatments: WT 1. Rituximab (with solumedrol), 2015 32% C481R 2. Ibrutinib, 2015-2021 41% Disease at Study Entry: L528W Bone
Slide 21: Clinical Response Observed in Patient 1
Clinical Response Observed in Patient 1 Safety Exposure No dose interruptions or modifications DLT’s None SAE’s None Absolute Lymphocyte Count 60 Grade 3 or > AE Neutropenia (ANC = 860), resolved without intervention Cell Count (K/uL) 40 Disease Assessment Lymph Nodal Time Hgb Plt ALC Spleen Spleen
Slide 22: Preliminary Findings: Robust Degradation of BTK by NX-2127 in All Patients Dosed
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 ad
Slide 23: Conclusions
Conclusions 1. Nurix protein modulation pipeline now has two programs in clinical development: NX-2127 (TPD) and NX-1607 (ligase inhibition) with two more programs advancing 2. Robust BTK degradation demonstrated by NX-2127 in patients validates Nurix’s BTK portfolio approach in targeted protein deg
Slide 24: Questions and Answers
(] nN U rix Questions and Answers
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