Nurix Therapeutics, Inc. · NASDAQ:NRIX
Nurix Therapeutics — American Society of Hematology Investor Event 2024
44 slides from Nurix Therapeutics's conference presentation, Dec 10, 2024
Slide 1: Nurix Therapeutics: Blazing a New Path in Medicine
Nurix Therapeutics Blazing a New Path in Medicine American Society of Hematology Investor Event December 9, 2024 Exhibit 99.2
Slide 2: Important Notice and Disclaimers
2 Important Notice and Disclaimers 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 “antici
Slide 3: ASH 2024: Three abstracts on Nurix BTK degraders
3 ASH 2024 Three abstracts on Nurix BTK degraders, including two oral presentations Program Title Authors Abst # Presentation NX-5948 Efficacy and Safety of the Bruton’s Tyrosine Kinase (BTK) Degrader NX-5948 in Patients with Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia (CLL): Updated Resu
Slide 4: Agenda
NX-5948: Efficacy and safety of NX-5948 in patients with relapsed/refractory chronic lymphocytic leukemia NX-5948: Preliminary findings in patients with Waldenstrom’s Macroglobulinemia Nirav N. Shah, M.D., MSHP Associate Professor of Medicine, Division of Hematology and Oncology, Medical College of
Slide 5: Efficacy and safety of BTK degrader NX-5948 in relapsed/refractory CLL
Efficacy and safety of the Bruton’s tyrosine kinase (BTK) degrader NX-5948 in patients with relapsed/refractory chronic lymphocytic leukemia: updated results from an ongoing Phase 1a/b study Nirav N. Shah, Zulfa Omer, Graham Collins, Francesco Forconi, Alexey Danilov, John C. Byrd, Dima El Sharkawi,
Slide 6: Background: NX-5948 addresses unmet need in CLL treatment
• The current standard of care in CLL focuses on utilizing the inhibitors of two key signaling pathways – BTK and BCL2 • Unmet need still exists in the CLL treatment landscape: – Covalent and non-covalent BTKi resistance mutations1 are found in more than half of patients who progress on BTKi therapi
Slide 7: NX-5948-301: Trial Design
Phase 1a dose escalation (completed enrollment) Phase 1b dose expansion (N = up to 160 patients) Key eligibility criteria • Age ≥18 years • Relapsed/refractory disease • ≥2 prior lines of therapy (≥1 for PCNSL) • ECOG PS 0–1 (ECOG PS 0–2 for PCNSL) 50 mg QD 100 mg QD 200 mg QD 300 mg QD 450 mg QD 60
Slide 8: CLL Patient Disposition and Demographics
8 CLL Patient Disposition and Demographics Phase 1a and 1b CLL, chronic lymphocytic leukemia; SLL, small lymphocytic lymphoma Dosed (n=60) 50 mg: n=3 100 mg: n=5 200 mg: n=14 300 mg: n=8 450 mg: n=7 600 mg: n=23 CLL/SLL (n=60) Discontinued treatment (n=14) Radiological progression: n=5 Clinical prog
Slide 9: Baseline Disease Characteristics
9 Baseline Disease Characteristics Multiple prior lines of therapy and high prevalence of baseline mutations Characteristics Patients with CLL/SLLa (n=60) ECOG PS, n (%) 0 1 24 (40.0) 36 (60.0) CNS involvement, n (%) 5 (8.3) Median prior lines of therapy (range) 4.0 (1–12) Previous treatmentsb, n (%
Slide 10: NX-5948 Safety Profile
10 NX-5948 Safety Profile TEAEs in ≥10% of overall population or Grade ≥3 TEAEs or SAEs in >1 patient aPurpura/contusion includes episodes of contusion or purpura; bFatigue was transient; cAggregate of ‘thrombocytopenia’ and ‘platelet count decreased’; dAggregate of ‘rash’ and ‘rash maculopapular’ a
Slide 11: NX-5948 Degrades Wild-Type and Mutated BTK
11 NX-5948 Degrades Wild-Type and Mutated BTK NX-5948 degrades gatekeeper, kinase-proficient and kinase-dead BTK mutations Patients with CLL/SLL (n=57)c Baseline mutation status, n (%) BTK mutations1,a,b 22 (38.6) C481S 12 (21.1) C481R 2 (3.5) L528W 4 (7.0) L528S 1 (1.8) T474I 5 (8.8) T474F 1 (1.8)
Slide 12: NX-5948 Overall Response Assessment
NX-5948 Overall Response Assessment Response rate deepens with longer time on treatment CLL response-evaluable patients Primary ORR analysisb ≥1 response assessment(s) at 8 weeks (n=49)c Exploratory ORR analysisb ≥2 response assessments at 16 weeks (n=38)c Objective response rate (ORR),a % (95% CI)
Slide 13: Lymph Node Assessment and High-Risk Molecular Features
*Patient with Richter’s transformation to Hodgkin's on biopsy Note: patients without identified target lesion(s) at baseline are evaluated as disease-evaluable per iwCLL criteria, while they may not be represented in waterfall plot ATM, Ataxia-telangiectasia mutated; BTK, Bruton’s tyrosine kinase; B
Slide 14: NX-5948 Duration of Treatment
14 NX-5948 Duration of Treatment Durable responses regardless of prior therapy BCL2i, BCL2 inhibitor; BTKi, BTK inhibitor; cBTKi, covalent BTKi; CIT, chemo/chemo-immunotherapies; ncBTKi, non-covalent BTKi; PD, progressive disease; PR, partial response; PR-L, PR with rebound lymphocytosis; SD, stable
Slide 15: Conclusions
• In this ongoing Phase 1 study, the BTK degrader NX-5948 demonstrated an encouraging clinical profile in a heavily pre-treated population of patients with CLL • NX-5948 was well tolerated across B-cell malignancies, with no additional safety signals observed with longer duration on study or increas
Slide 16: NX-5948: Preliminary findings in Waldenstrom's macroglobulinemia
NX-5948: Preliminary findings in patients with Waldenstrom’s macroglobulinemia 16 Highlights from the International Workshop on Waldenstrom's Macroglobulinemia (IWWM) in October 2024
Slide 17: NX-5948-301: Trial Design
Phase 1a dose escalation (completed enrollment) Phase 1b dose expansion (N = up to 160 patients) Key eligibility criteria • Age ≥18 years • Relapsed/refractory disease • ≥2 prior lines of therapy (≥1 for PCNSL) • ECOG PS 0–1 (ECOG PS 0–2 for PCNSL) 50 mg QD 100 mg QD 200 mg QD 300 mg QD 450 mg QD 60
Slide 18: Baseline Demographics/Disease Characteristics
Baseline Demographics/Disease Characteristics Elderly population with multiple prior lines of targeted therapies Characteristics Patients with WM (n=13) Median age, years (range) 74.0 (64–82) Male, n (%) 11 (84.6) ECOG PS, n (%) 0 1 3 (23.1) 10 (76.9) CNS involvement, n (%) 0 Median prior lines of t
Slide 19: NX-5948 Efficacy and Duration of Treatment in Patients with WM
NX-5948 Efficacy and Duration of Treatment in Patients with WM Data cutoff: 10 Oct 2024 Select prior therapies Select mutations BTKi BCL2i Pirto CXCR4 MYD88 WM disease-evaluable patients n=9 ORR, % 77.8 Best response, n (%) CR 0 (0.0) PR / MR 7 (77.8) SD 2 (22.2) PD 0 (0.0) *Ineligible, identified p
Slide 20: Steady Decrease in IgM Levels in Patients Treated with NX-5948
Steady Decrease in IgM Levels in Patients Treated with NX-5948 Percent change in IgM levels from baseline in patients with WM1 Data cutoff: 10 Oct 2024 #Transformed to DLBCL 1Response criteria used: Owen RG, Kyle RA, Stone MJ, et al. VIth International Workshop on Waldenström macroglobulinaemia. Res
Slide 21: Conclusions – Waldenstrom's Macroglobulinemia
• NX-5948 was administered to 13 WM patients with a median of 3 prior lines of therapy, all of whom had been treated previously with both chemotherapy and BTK inhibitors • NX-5948 is well tolerated in WM patients, consistent with the overall NHL and CLL populations • Highly encouraging overall respo
Slide 22: NX-5948: Advancing into pivotal development in 2025
NX-5948: Advancing into pivotal development in 2025 22 Regulatory update and development plans in CLL
Slide 23: NX-5948 Regulatory Milestones
• U.S. Fast Track Designation from the FDA in January 2024 • CLL Type B End of Phase 1 meeting held with the FDA, key takeaways: • Reviewed dose levels of 200 mg QD and 600 mg QD in the context of Project Optimus • Helpful feedback on principles of pivotal trial designs including Fast Track populati
Slide 24: Accelerating Development of NX-5948 in CLL with First Pivotal Study in 2025
Nurix Is Accelerating Development of NX-5948 in CLL with First Pivotal Study To Be Initiated in 2025 • Clear demonstration of clinical activity in difficult to treat CLL population • Phase 1b cohorts enrolling rapidly with post- BTKi/post-BCL2i CLL patients randomized between 200mg QD and 600mg QD •
Slide 25: Section I: Q&A
Section I: Q&A 25
Slide 26: NX-1607 and NX-2127: Clinical updates and next steps
NX-1607 and NX-2127 26 Clinical updates and next steps
Slide 27: NX-1607: Phase 1a/b Trial in Advanced Solid Tumors
NX-1607: Phase 1a/b Trial in Patient with Advanced Solid Tumors Extensive exploration of dose and schedule to optimize tolerability and PD effects Phase 1a Monotherapy Dose Escalation Potential Phase 1b Monotherapy Dose Expansion Cohorts Key eligibility criteria • Age ≥18 years • Metastatic/unresect
Slide 28: Dose Dependent Increase in Proximal Biomarker Supports BID Dosing
Dose Dependent Increase in Proprietary Proximal Biomarker Supports Benefit of Twice Daily Dosing Data cutoff: 22 November 2024 • Inhibition of CBL-B by NX-1607 blocks degradation of substrate proteins and enhances signaling through the T cell receptor • Elevation of phosphorylated HS1 (pHS1) serves
Slide 29: NX-1607 Status and Next Steps
29 NX-1607 Status and Next Steps Status • Phase 1a has enrolled 66 heavily pretreated patients across 11 different solid tumor indications • Oral dosing of NX-1607 has been associated with gastrointestinal tolerability issues that have been mitigated through exploration of ramp-up dosing, BID regime
Slide 30: NX-2127: Phase 1a/b Trial in Relapsed/Refractory B-cell Malignancies
30 NX-2127: Phase 1a/b Trial in Relapsed/Refractory B-cell Malignancies Enrollment ongoing in dose escalation with new drug product Phase 1a Dose Escalation Phase 1b Monotherapy Expansion Cohorts (no longer enrolling new patients) Key eligibility criteria • Age ≥18 years • Relapsed/Refractory diseas
Slide 31: Updated Clinical Case Study: WM transformed to DLBCL
Updated Clinical Case Study 1 Rapid and sustained complete response in WM transformed to DLBCL with NX-2127 Confirmatory Week 16 scan Deauville score: 2 Baseline FDG-PET CT Scan Disease Assessment Deauville score: 5 Bladder Bladder • 84-year-old female with WM diagnosed in 2003 with DLBCL (ABC subty
Slide 32: Updated Clinical Case Study 2: Relapsed/refractory MCL
Updated Clinical Case Study 2: Rapid and sustained complete response in relapsed/refractory MCL with NX-2127 32 Week 8 Scan Deauville score: 2 Baseline FDG-PET CT Scan Disease Assessment Deauville score: 5 Bladder Bladder • 64-year-old woman with multiply relapsed MCL, following: • 2016: Rituximab +
Slide 33: NX-2127 Status and Next Steps
33 NX-2127 Status and Next Steps Status • We have re-initiated enrollment with the new, chirally controlled drug product • We are focused on the aggressive lymphomas for development of NX-2127 where the combination of BTK degradation and IKZF1/3 degradation have the potential for synergy and signifi
Slide 34: NX-5948 in inflammation and immunology (I&I)
NX-5948 in inflammation and immunology (I&I) 34 Rationale & strategy
Slide 35: Key Observations Underpinning NX-5948 I&I Strategy
Key Observations Underpinning Nurix’s NX-5948 Immunology and Inflammation Strategy The genetics of BTK are compelling: highly specific with potent biology • Human knockouts, originally described by Dr. Bruton in 1952, show agammaglobulinemia (no antibody production) and associated reduced immune f
Slide 36: NX-5948 Is 10x to 100x More Potent in Blocking B Cell Activation
36 NX-5948 Is 10x to 100x More Potent in Blocking B Cell Activation than BTK Inhibitors Tested in I&I 0.001 0.01 0.1 1 10 100 1000 -75 -50 -25 0 25 50 75 100 125 Compound (nM) N or m al iz ed C D 69 NX-5948 Rilzabrutinib Remibrutinib Acalabrutinib Fenebrutinib Bead-Bound Anti-IgM Stimulation B Ce ll
Slide 37: NX-5948 Potently Suppresses Activation of Myeloid Cells
• IL-8 is a chemokine that recruits neutrophils into inflamed tissues 37 NX-5948 Potently Suppresses Activation of Myeloid Cells Stimulated Through Key Inflammatory Receptors 0.001 0.01 0.1 1 10 100 1000 0.00 0.25 0.50 0.75 1.00 1.25 Compound (nM) IL -8 F ol d C ha ng e NX-5948 Rilzabrutinib Remibru
Slide 38: NX-5948 Is Active Across Autoimmune and Inflammation Models
NX-5948 Is Active Across a Range of Autoimmune and Inflammation Models 38 Systemic Lupus Erythematosus (MRL/Ipr Model) Lupus Nephritis (AIG Model) Multiple Sclerosis (EAE Model) Rheumatoid Arthritis (Established CIA Model) 10 12 14 16 18 20 0 1 2 3 Animal Age (Weeks) U rin e Pr ot ei n Sc or e M ea
Slide 39: NX-5948 Has the Right Clinical Profile for Oncology and I&I
NX-5948 Has The Right Clinical Profile To Address Unmet Clinical Needs in Both Oncology and I&I 39 Wide dose range produces robust BTK degradation Elimination of BTK’s scaffolding function Demonstrated ability to cross the blood-brain barrier Favorable safety profile in oncology clinical trials 0 20
Slide 40: NX-5948 I&I Vision: First BTK Degrader with Practice Changing Potential
NX-5948 I&I Vision: Introduce the First BTK Degrader with Practice Changing Potential Strategic considerations for introducing NX-5948 into immunology and inflammation: 1. Novel mechanism of action: First BTK degrader in I&I should be focused on areas where BTK has strong biologic rationale and an a
Slide 41: Nurix's Systematic Approach To Expand NX-5948 Across I&I Indications
Goal: Implement a sequenced, multi-organ system approach to generate the greatest opportunity for patients and value creation 1. Hematology: Leverage Nurix’s existing hematology expertise, seeking first proof of concept through study of CLL patients with secondary autoimmune-mediated hemolytic anemi
Slide 42: Implementing Nurix's Systematic Approach to I&I
Next Steps: 1. Plan to open a new Phase 1b cohort for patients with CLL and associated autoimmune hemolytic anemia in H1 2025 2. Plan non-malignant hematology IND in 2025 for autoimmune cytopenias (e.g., wAIHA) 3. Conduct a healthy volunteer study of a new formulation to address potential need for b
Slide 43: Nurix: Building Blocks of Success and Value Creation
43 Nurix: Building Blocks of Success and Value Creation Drive NX-1607 and NX-2127 to proof-of-concept data Successfully execute NX-5948 development in CLL A core opportunity with Fast Track and Prime Designation, we are moving rapidly to pivotal trials in 2025 Advance our innovative degrader pipelin
Slide 44: Section II: Q&A
Section II: Q&A 44
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