Nurix Therapeutics, Inc. · NASDAQ:NRIX
Nurix Therapeutics — Technical Presentation (June 2024)
32 slides from Nurix Therapeutics's technical presentation, Jun 17, 2024
Slide 1: NX-5948 Clinical Update, EHA2024
Nurix Therapeutics NX-5948 Clinical Update European Hematology Association Congress EHA2024 June 16, 2024
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: Agenda
Agenda I. Introduction Arthur T. Sands, MD, PhD Chief Executive Officer, Nurix Therapeutics II. NX-5948 clinical presentation from EHA Kim Linton, MBChB, MRCP, PhD, FRCP University of Manchester and The Christie NHS Foundation Trust III. Patient journey and program next steps Paula G. O’Connor, MD C
Slide 4: Nurix Is Advancing a Pipeline of Proprietary and Partnered Programs
MOA Oncology program Target Therapeutic area Discovery – Lead Op IND enabling Phase 1a Phase 1b TPD NX-5948 BTK B-cell malignancies NX-2127 BTK-IKZF B-cell malignancies TPE NX-1607 CBL-B Immuno-Oncology TPD Multiple Undisclosed Undisclosed Multiple Undisclosed Undisclosed Multiple Undisclosed Undisc
Slide 5: Executive Summary: NX-5948, an emerging best-in-class profile in CLL
• NX-5948 has demonstrated positive results from the ongoing Phase 1a clinical trial in patients with an objective response rate of 69.2% in heavily pretreated CLL patients including those with BTK inhibitor resistance mutations • Clinical responses in CLL patients were rapid and deepening with long
Slide 6: Kim Linton, University of Manchester and The Christie
Kim Linton, MBChB, MRCP, PhD, FRCP University of Manchester and The Christie NHS Foundation Trust 6
Slide 7: Latest Results from Ongoing First-in-Human Phase 1a/b Study of NX-5948
Latest Results from an Ongoing First-in-Human Phase 1a/b Study of NX-5948, a Selective Bruton’s Tyrosine Kinase (BTK) Degrader, in Patients with Relapsed/Refractory CLL and Other B-cell Malignancies Kim Linton, Graham P. Collins, Francesco Forconi, Nirav N. Shah, Karan Dixit, Talha Munir, Zulfa Omer
Slide 8: Unmet Clinical Need: Relapsed/Refractory CLL
• Targeted therapy focusing on two key pathways (BTK/BCL2) is standard of care in CLL and has changed the treatment landscape in front-line and relapsed/refractory settings • Emerging patterns of resistance limit the utility of currently available therapies: – BTK mutations confer resistance to both
Slide 9: NX-5948 Mechanism of Action
9 NX-5948 Mechanism of Action Utilize the ubiquitin-proteasome pathway to degrade BTK, a well-validated target in B-cell malignancies BTK degraders can overcome treatment-emergent resistance mutations BTK degraders have the potential to replace BTK inhibitors in the clinic BTK degraders show emergin
Slide 10: NX-5948-301: Trial Design
NX-5948-301: Trial Design Phase 1a/b trial in adults with relapsed/refractory B-cell malignancies Phase 1a dose escalation Potential 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) • EC
Slide 11: Patient Disposition
Screened (N=121)a Screen failure (n=39) Patient Disposition Patients were dosed in CLL (n=31) and NHL/WM (n=48) dose-escalation cohorts aIncludes 3 patients at screening but not yet enrolled on study at time of data cutoff; bPercent of total patient population Data cutoff: 17 April 2024 Dosed (n=31)
Slide 12: Baseline Demographics/Disease Characteristics
Baseline Demographics/Disease Characteristics Elderly population with multiple prior lines of targeted therapies Characteristics Patients with CLL (n=31) Patients with NHL/WM (n=48) Overall population (N=79) Median age, years (range) 69.0 (35–88) 66.5 (42–87) 67.0 (35–88) Male, n (%) 19 (61.3) 33 (6
Slide 13: NX-5948 Is Well Tolerated
NX-5948 Is Well Tolerated TEAEs in ≥10% of overall population or grade ≥3 TEAEs or SAEs in >1 patient Patients with CLL (n=31) Overall population (N=79) TEAEs, n (%) Any grade Grade ≥3 SAEs Any grade Grade ≥3 SAEs Purpura/contusiona 13 (41.9) – – 28 (35.4) – – Thrombocytopeniab 7 (22.6) 1 (3.2) – 21
Slide 14: NX-5948 Efficacy: Clinical Response
NX-5948 Efficacy: Clinical Response Broad antitumor activity in CLL as demonstrated by significant lymph node reduction and ORR 14Data cutoff: 17 April 2024SPD, sum of products diameters; CR, complete response; CRi, complete response with incomplete marrow recovery; PR, partial response; nPR, nodula
Slide 15: NX-5948 Efficacy: Duration of Treatment
15 NX-5948 Efficacy: Duration of Treatment Durable responses seen in heavily pretreated patients with CLL BCL2i cBTKi ncBTKi ≥2 prior BTKi Select prior therapies * *Patient with Richter’s transformation to Hodgkin's on biopsy Median duration of treatment, months (range) 2.8 (0.2–15.2) Patients dose
Slide 16: Case Study: Patient with CLL and CNS Involvement
0 10 20 30 40 50 60 0 50 100 150 200 250 300 Ce ll Co un ts (K /µ L) Study day ALC 16 16 weeks: Partial Response LN: –64% (>50% PR) Spleen: –68% (>50% PR) Plts: >100 (CR) Hgb: >11 g/dL (CR) Malignant cells in CSF: Y Case Study: Patient with CLL and CNS Involvement Deepening response over time approa
Slide 17: Mutation Status and BTK Degradation
Mutation Status and BTK Degradation NX-5948 induces rapid and robust degradation of wild-type and mutant BTK 17 Patients with CLL (n=30) Mutation status, n (%) BTKa 13 (43.3) C481S 7 (23.3) L528b 2 (6.7) T474c 3 (10.0) V416d 1 (3.3) G541V 1 (3.3) aPatients could have multiple BTK mutations; BTK muta
Slide 18: Clinical Activity in Patients with Baseline Mutations
18 Clinical Activity in Patients with Baseline Mutations Treatment resistance and poor-prognosis genetic mutations *Patient with Richter’s transformation to Hodgkin's on biopsy • Baseline treatment-resistance and poor prognosis mutations were common, indicating a genetically diverse and hard-to-trea
Slide 19: Clinical Activity in Patients with Baseline Mutations
19 Clinical Activity in Patients with Baseline Mutations Treatment resistance and poor-prognosis genetic mutations • Baseline treatment-resistance and poor prognosis mutations were common, indicating a genetically diverse and hard-to-treat CLL patient population • No genotypic profile was linked to
Slide 20: Conclusions
• NX-5948 was well tolerated in patients with NHL and CLL, with no increased safety signal at higher doses • Deep and durable clinical responses were observed in a difficult-to-treat CLL patient population: – Heavily pretreated patient population with unfavorable genetic mutations associated with po
Slide 21: Paula G. O'Connor, Chief Medical Officer
Paula G. O’Connor, MD Chief Medical Officer Nurix Therapeutics 21
Slide 22: NX-5948: The Patient Journey
Two additional case studies highlighting the activity of NX-5948 to address patients with high unmet medical needs NX-5948: The Patient Journey
Slide 23: Case Study 1: CLL Patient with Extensive Prior Treatment
Relevant Medical History • Atrial fibrillation: Dx Jul 2022 • Hypothyroidism: Dx May 2022 • Hypertension: Dx Jul 2022 • Fatigue: Dx Oct 2023 • Disease related cytopenias: Dx 2022-23 Molecular, Cytogenetics and other baseline features • Del(11q, 13q)*, IGHV unmutated* • BTK T474I mutation** • Bulky d
Slide 24: Case Study 1: Rapid and sustained lymph node reduction
0 5 10 15 20 25 0 20 40 60 80 100 120 140 160 180 200 Ce ll Co un t ( K/ uL ) Study Day ALC 24Data cutoff: 31 May 2024 Case Study 1: CLL Patient with Extensive Prior Treatment Rapid and sustained lymph node reduction with improving hematologic features Baseline LN SPD: 163.2 cm2 Spleen: 16.1 cm (abn
Slide 25: Case Study 2: CLL Patient with High-Risk Features
25 Relevant Medical History • Supraventricular tachycardia: Jun 2018 - present • Peripheral neuropathy: Oct 2018 - present • Hearing loss: Apr 2008 - present • Tinnitus: Apr 2008 - present • Chronic kidney disease: Jul 2019 – present Prior Systemic Therapies • Campath + rituximab: Nov 2008 – Mar 200
Slide 26: Case Study 2: Early clinical activity deepening over time
0 20 40 60 80 100 120 140 160 180 0 20 40 60 80 100 120 140 160 180 200 Ce ll Co un t ( K/ ul ) Study Day ALC 26 8 weeks: Partial Response LN: -59% ( > 50% PR) Spleen: -68% (> 50% PR) Plts: 332 K/µl (Normal) Hgb: + 21% (SD) Initial lymphocytosis consistent with BTK targeted MOA.*Normal spleen= <13 c
Slide 27: NX-5948: Next Steps in CLL
NX-5948: Next Steps in CLL
Slide 28: Next Steps: Expand Phase 1b in Select CLL Populations
Next Steps: Expand Phase 1b in Select CLL Populations Enable Pivotal Trial Initiation in 2025 Phase 1b expansion in CLL Pivotal trials in 3L+ CLLCLL/SLL (n = 80-160) Two monotherapy dose levels to be selected from Phase 1a dose escalation Includes multiple cohorts in clinically meaningful population
Slide 29: Conclusions: Nurix Plans To Accelerate Development of NX-5948
Conclusions: Nurix Plans To Accelerate Development of NX-5948 with First Pivotal Study To Be Initiated in 2025 CLL: Clear demonstration of clinical activity in difficult to treat populations • Advancing to an expanded Phase 1b across a wide range of CLL subpopulations • Preparing for initiation of
Slide 30: Arthur T. Sands, Chief Executive Officer
Arthur T. Sands, MD, PhD Chief Executive Officer Nurix Therapeutics 30
Slide 31: Nurix Therapeutics: Planning for Success
Nurix Therapeutics: Planning for Success We believe NX-5948 is a potential best-in-class drug that can replace BTK inhibitors and offer patients important treatment options We have a team that can successfully accelerate development to move to pivotal trial(s) in 2025 We have built a robust an
Slide 32: Questions & Answers
Questions & Answers 32
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