Slide 1: Nurix Therapeutics: Blazing a New Path in Medicine
Nurix Therapeutics Blazing a New Path in Medicine ASH Event Presentation December 11, 2023
Slide 2: Important Notice and Disclaimers
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 “anticipa
Slide 3: A First-In-Class Franchise of BTK Degraders
A First-In-Class Franchise of BTK Degraders NX-5948 & NX-2127 – The big picture NX-5948 SELECTIVE BTK BTK degraders have the potential to displace inhibitors DEGRADATION NX-2127 BTK degraders can overcome treatment emergent BTK DEGRADATION & IMMUNOMODULATION resistance mutations BTK degraders may ex
Slide 4: Blockbuster Opportunity in BTK Market
Blockbuster Opportunity in BTK Market $8.4 billion in annual sales BTK Yearly Sales • Next generation BTK inhibitors are 9000 currently taking market 8000 share from Imbruvica 7000 6000 • All BTK inhibitors share resistance mutation 5000 vulnerabilities 4000 3000 • Opportunity for Nurix 2000 BTK deg
Slide 5: Evolution of BTK Targeted Therapies
Evolution of BTK Targeted Therapies Degraders Non-Covalent Inhibitors NX-5948 Resistance NX-2127 Is Futile Next Generation Pirtobrutinib Covalent inhibitors 1st Generation Acalabrutinib Covalent inhibitor Zanubrutinib Ibrutinib 5
Slide 6: NX-5948 Is More Potent and Broadly Active Than All BTK Inhibitors Tested
NX-5948 Is More Potent and Broadly Active Than All BTK Inhibitors Tested Broad Preclinical Activity 8W 1S L GI-50 (nM) 4I 16 48 7 2 T • All inhibitors have resistance V4 T4 L5 W C Most potent 0 mutation liabilities NX-5948 cell killing 1st Generation Ibrutinib 1000 • NX-5948 displays potent cell kil
Slide 7: ASH 2023: Building the Degrader Story with Positive Clinical Data
ASH 2023: Building the Degrader Story with Positive Clinical Data NX-5948 NX-2127 SELECTIVE BTK DEGRADATION BTK DEGRADATION & IMMUNOMODULATION • Positive preliminary efficacy data in • Positive update on CLL cohort with CLL with responses seen at all dose improving efficacy and manageable levels and
Slide 8: Tonight's Agenda
Tonight’s Agenda ASH 2023 Clinical Updates for NX-2127 and NX-5948 A first-in-human phase 1 trial of NX-2127, a first-in- Alexey Danilov, M.D., Ph.D. class Bruton's Tyrosine Kinase (BTK) dual-targeted Professor, Division of Leukemia, protein degrader with immunomodulatory activity, and Associate Dir
Slide 9: A First-In-Human Phase 1 Trial of NX-2127
A First-In-Human Phase 1 Trial of NX-2127, a First-In-Class Bruton's Tyrosine Kinase (BTK) Dual-Targeted Protein Degrader With Immunomodulatory Activity, in Patients With Relapsed/Refractory B-cell Malignancies 1Alexey Danilov, 2Michael Tees, 3Krish Patel, 4William Wierda, 5Manish R. Patel, 6Ian Fli
Slide 10: NX-2127 Dual Mechanism of Action
NX-2127 Dual Mechanism of Action: Degradation of BTK and IKZF1/3 – Targeting B-cells and engaging T cells BCR, B-cell receptor; BTK, Bruton’s tyrosine kinase; CRBN, cereblon; IFN, interferon; IL, interleukin 10
Slide 11: NX-2127-001: Trial Design
NX-2127-001: Trial Design Phase 1a/b trial in adults with relapsed/refractory B-cell malignancies Phase 1a • NX-2127-001 (NCT04830137) Phase 1b Accelerated titration / 3+3 escalation (n∼60a) is a first-in-human, multicenter, Select cohort expansionb CLL/SLL, MCL, DLBCL, FL, MZL, WM U.S.-based, open-
Slide 12: Baseline Demographics and Disease Characteristics
Baseline Demographics and Disease Characteristics Heavily pretreated population with significant acquired resistance mutations NHL/WM CLL/SLL Overall population Characteristic (n=21) (n=33) (N=54) Median age, years (range) 70.0 (50.0–92.0) 74.0 (58.0–90.0) 72.5 (50.0–92.0) Female, n (%) 6 (28.6) 11
Slide 13: Baseline Demographics and Disease Characteristics (Cont'd)
Baseline Demographics and Disease Characteristics (Cont’d) Heavily pretreated population with significant acquired resistance mutations NHL/WM CLL/SLL Overall population Mutationa (n=21) (n=33) (N=54) BTK, n (%) 3 (14.3) 12 (36.4) 15 (27.8) C481S or C481R 1 (4.8) 7 (21.2) 8 (14.8) L528W 1 (4.8) 4 (1
Slide 14: NX-2127 Rapid, Robust and Sustained BTK Degradation
NX-2127 Treatment Results in Rapid, Robust and Sustained BTK Degradation With Clinically Relevant Ikaros Degradation A) NX-2127 C1D1 pharmacokinetics B) BTKa degradation in patients receiving NX-2127 C) Ikarosb degradation in patients receiving NX-2127 100 mg 200 mg 300 mg 1 2 0 0 0 100 100 100 plas
Slide 15: Safety Profile Manageable With Decreasing Incidence of Atrial Fibrillation
Safety Profile Manageable With Decreasing Incidence of Atrial Fibrillation Frequency of TEAEs in ≥20% of patients or grade ≥3 or SAEs in >1 patient, (n=54) Treatment emergent adverse Any grade Grade ≥3 SAEs events (TEAEs), n (%) Fatigue 25 (46.3) – – Neutropeniaa 25 (46.3) 23 (42.6) – Hypertens
Slide 16: Broad Antitumor Activity in CLL/SLL
Broad Antitumor Activity in CLL/SLL as Demonstrated by Significant Lymph Node Reduction and Objective Response Rate CLL/SLL disease-evaluable patientsa n=27 Objective response rateb, % (95% CI) 40.7 (22.4–61.2) 80 Best response, n (%) Percent Change in Lymph Node Size Maximum percentage change from
Slide 17: Durable Responses Seen in Heavily Pretreated CLL/SLL Patients
Durable Responses Seen in Heavily Pretreated CLL/SLL Patients NX-2127 NX-2127: TimeTime on study on study for CLL/SLL for patients subjects with CLL/SLL * All patients had prior cBTKi * * * Double exposed: Prior cBTKi and BCL2i Triple exposed: Prior cBTKi, ncBTKi, and BCL2i * Assigned Dose (mg) Resp
Slide 18: Responses Observed Across NHL Subtypes
Responses Observed Across NHL Subtypes Including Rapid and Sustained Complete Responses 440 PD NHL/WM disease-evaluable patientsa n=17 Best response, n (%) Percent Change in Lymph Node Size CR 2 (11.8) • Rapid CR at 8 80 PR 2 (11.8) Maximum percentage change from baseline in SPD weeks observed SD 5
Slide 19: Ongoing Durable Complete Responses in DLBCL and MCL
Ongoing Durable Complete Responses With Over One Year of Follow Up Seen in DLBCL and MCL NX-2127: TimeTime NX-2127 on study for patients on study with NHL for CLL/SLL subjects MCL DLBCL WM MZL FL MCL DLBCL MZL MCL MCL MZL FL MCL DLBCL DLBCL MCL MCL WM WM DLBCL DLBCL 0 1 2 3 4 5 6 7 8 9 10 11 12 13 1
Slide 20: Rapid and Sustained Complete Response in Relapsed/Refractory DLBCL
Rapid and Sustained Complete Response in Relapsed/Refractory DLBCL With NX-2127 FDG-PET CT Scan Disease Assessment Baseline Confirmatory Week 16 Scan Bladder Bladder • 84-year-old woman with multiply relapsed ABC- DLBCL following 4 lines of aggressive therapy (including combination of rituximab, ibr
Slide 21: Rapid and Sustained Complete Response in Relapsed/Refractory MCL
Rapid and Sustained Complete Response in Relapsed/Refractory MCL With NX-2127 FDG-PET CT Scan Disease Assessment Baseline Week 8 Scan Bladder Bladder • 64-year-old woman with multiply relapsed MCL, following stem cell transplant, chemo- immunotherapy, and ibrutinib • Complete response on first asses
Slide 22: NX-2127 Conclusions
NX-2127 Conclusions • NX-2127 has a manageable safety profile that is consistent with previous reports for BTK-targeted and immunomodulatory therapies, and consistent with prior disclosures • Treatment with NX-2127 resulted in encouraging and durable responses in a heavily pre-treated patient popula
Slide 23: Initial Findings From a First-In-Human Phase 1a/b Trial of NX-5948
Initial Findings From a First-In-Human Phase 1a/b Trial of NX- 5948, a Selective Bruton’s Tyrosine Kinase (BTK) Degrader, in Patients With Relapsed/Refractory B Cell Malignancies 1Emma Searle, 2Francesco Forconi, 1Kim Linton, 3Alexey Danilov, 4Pam McKay, 5David Lewis, 6Dima El-Sharkawi, 7,8Mary Glee
Slide 24: NX-5948 Mechanism of Action
NX-5948 Mechanism of Action: Targeted degradation of BTK BTK destroyed by Nurix the proteasome degrader E2 Ubiquitin drugs BTK Degrader Cereblon recycling E3 ligase BTK complex BTK Poly ubiquitinated proteins Ubiquitination of protein 24
Slide 25: 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 expansiona B-cell malignancies, including CLL (N = up to 30 patients) (N = up to 80 patients) Dose L6+ CLL/SLL (n=20) 600 mg QD Prior BTKi and BCL-2i Dos
Slide 26: Baseline Demographics and Disease Characteristics
Baseline Demographics and Disease Characteristics Heavily pretreated population Patients with CLL Patients with NHL/WM Overall population Characteristics (n=7) (n=19) (N=26) Median age, years (range) 64.0 (53–75) 63.0 (42–79) 63.5 (42–79) Male, n (%) 5 (71.4) 13 (68.4) 18 (69.2) Female, n (%) 2 (28.
Slide 27: NX-5948 Rapid, Robust and Sustained BTK Degradation
NX-5948 Treatment Results in Rapid, Robust and Sustained BTK Degradation A) NX-5948 C1D1 pharmacokinetics B) BTKa degradation in patients receiving NX-5948 5 0 50 mg (n=7) 12000 50 mg plasma concentration (ng/mL) 100 mg (n=6) 10000 (background subtracted) NX-5948 mean (±SEM) 4 0 100 mg 200 mg (n=6)
Slide 28: NX-5948 Was Well Tolerated
NX-5948 Was Well Tolerated Frequency of TEAEs in ≥15% of patients or grade ≥3 or SAEs in >1 patient, (n=26) TEAEs, n (%) Any grade Grade ≥3 SAEs Purpura/contusiona 12 (46.2) – – Thrombocytopeniab 10 (38.5) 2 (7.7) – Neutropeniac 8 (30.8) 5 (19.2) – Anemia 6 (23.1) 1 (3.8) – Cough 5 (19.2) – – Headac
Slide 29: NX-5948 Was Well Tolerated Across Doses Tested
NX-5948 Was Well Tolerated Across Doses Tested Frequency of any grade TEAEs in ≥15% of patients 50 mg 100 mg 200 mg 300 mg 450 mg All doses TEAEs, n (%) (n=7) (n=6) (n=6) (n=4) (n=3) (N=26) Purpura/contusiona 5 (71.4) 2 (33.3) 1 (16.7) 2 (50.0) 2 (66.7) 12 (46.2) Thrombocytopeniab 2 (28.6) 3 (33.3)
Slide 30: Broad Antitumor Activity in CLL
Broad Antitumor Activity in CLL as Demonstrated by Significant Lymph Node Reduction and Objective Response Rate CLL disease-evaluable patientsa n=7 80 Objective response rateb, % (95% CI) 42.9 (9.9–81.6) Maximum Percent Change from Baseline in Sum of Product Diameters • 6/7 patients showed clinical
Slide 31: Rapid and Deepening Nodal Reductions in CLL Patients
Rapid and Deepening Nodal Reductions in CLL Patients 100 Dose Response of target lesions 80 50 mg PR 100 mg SD 60 200 mg PD An initial decrease in lymph node size was baseline 40 observed in all patients in SPD 20 regardless of best change from clinical response, with 0 % baseline the majority -20 d
Slide 32: Responses to NX-5948 Observed Across NHL Subtypes
Responses to NX-5948 Observed Across NHL Subtypes 260 MCL DLBCL NHL/WM disease-evaluable patientsa n=14 Maximum Percent Change from Baseline in Sum of Product Diameters PCNSL Best response, n (%) CR 0 (0.0) 80 PR/PMR 3 (21.4) SD 3 (21.4) 60 MCL PD 8 (57.1) Activity observed across aPatients without
Slide 33: Durable Responses Across Indications
Durable Responses Across Indications NX-5948: Time on study for patients with CLL and NHL CLL CLL CLL CLL CLL CLL CLL MZL DLBCL MZL MCL MCL DLBCL WM DLBCL FL PCNSL CLL, chronic lymphocytic leukemia; DLBCL, diffuse large B cell lymphoma; FL, Follicular MCL lymphoma; MCL, Mantle cell lymphoma; MZL, WM
Slide 34: NX-5948 Conclusions
NX-5948 Conclusions • NX-5948 PK exposure resulted in rapid, robust, and sustained BTK degradation • NX-5948 was well tolerated across 5 dose levels tested (50mg – 450mg daily) and escalation continues: − No atrial fibrillation/flutter or hypertension − No DLTs and no TEAEs resulting in drug discont
Slide 35: Next Steps and Future Vision
Next Steps and Future Vision 35
Slide 36: Nurix BTK Degrader Franchise: Two BTK Degraders to Cover B-Cell Malignancies
Nurix BTK Degrader Franchise: Two BTK Degraders to Cover the Landscape of B-Cell Malignancies B-Cell Malignancies Annual Incidence (U.S. & EU) NX-5948 NX-5948 NX-5948 potential in combination for all lines of therapy in CLL and Therapeutic goal: Displace BTKi in indications where single-agent Therap
Slide 37: Next Steps: Enable Broad Development Program Across B-Cell Malignancies
Next Steps: Enable Broad Development Program Across B-Cell Malignancies NX-5948: • Identify Phase 1b expansion dose levels for CLL and NHL with expansion planned for early 2024 • Enable combination trials with agents commonly used across B-cell malignancies • Enable a broad Phase 3 program across CL
Slide 38: Vision: Prioritizing NX-5948 in CLL and Enabling Broad Strategy in NHL
Vision: Prioritizing NX-5948 in CLL and Enabling Broad Strategy in NHL B-cell malignancies CLL MCL DLBCL Phase 1 & 2 Phase 3 Phase 3 Phase 3 Enable potential 2L+ CLL r/r MCL 1L DLBCL accelerated approval(s) Superiority post Superiority to BTKi Improve SOC in r/r CLL/MCL/WM BTKi +/- BCL-2i failure 1L
Slide 39: Beyond Hem/Onc: NX-5948 Is Potent in Inflammation and Immunology Models
Beyond Hem/Onc: NX-5948 Is Potent in Relevant Efficacy Models of Major Inflammation and Immunology Indications Rheumatoid Arthritis Model Multiple Sclerosis Model NX-5948 in 4 3 Clinical Arthritis Score EAE Severity Score 3 Inflammation & 2 Immunology 2 Tx * 1 1 ** * **** ** Plans to enable initiati
Slide 40: Vision: Focused Strategy With NX-2127 in NHL
Vision: Focused Strategy With NX-2127 in NHL B-cell malignancies DLBCL MCL Phase 1 & 2 Phase 3 Phase 3 Establish ORR and CR r/r DLBCL r/r MCL rate in DLBCL and MCL Potential monotherapy Potential monotherapy Enable combinations 1L DLBCL for earlier line trials Improve SOC Initiation of advanced deve
Slide 41: Nurix Is Advancing a Pipeline of Proprietary and Partnered Programs
Nurix Is Advancing a Pipeline of Propriety and Partnered Programs in Oncology and Autoimmune/Inflammatory Diseases MOA Drug program Target Therapeutic area Discovery IND enabling Phase 1a Phase 1b NX-2127 BTK-IKZF B-cell malignancies B-cell malignancies / NX-5948 BTK autoimmune disease NX-0479 / Rhe
Slide 42: Leadership and Value Creation
Leadership and Value Creation F O U N D AT I O N VA L U E D R I V E R S Scientific leadership in targeted Three wholly owned and internally developed protein modulation Phase 1 clinical assets World-class discovery capabilities Advancing multiple preclinical programs, with driven by our DELigase pla
Slide 43: Q&A
Q&A 43