Nurix Therapeutics, Inc. · NASDAQ:NRIX
Nurix Therapeutics — Investor Presentation (September 2024)
37 slides from Nurix Therapeutics's investor presentation, Sep 5, 2024
Slide 1: Leader in Targeted Protein Modulation: Blazing a New Path in Medicine
Leader in Targeted Protein Modulation Nurix Therapeutics Blazing a New Path in Medicine Investor Presentation September 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: Pipeline of Proprietary and Partnered Programs in Oncology and I&I
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 4: Why Do We Need BTK Degraders?
4 Why Do We Need BTK Degraders? BTK degraders can overcome treatment-emergent resistance mutations BTK degraders have the potential to replace BTK inhibitors in the clinic BTK degraders show emerging activity in various B-cell malignancies BTK degraders address BTK scaffolding function BTK: Bruton’s
Slide 5: NX-5948 Is More Potent and Broadly Active Than All BTK Inhibitors Tested
5 NX-5948 Is More Potent and Broadly Active Than All BTK Inhibitors Tested • All inhibitors have resistance mutation liabilities • NX-5948 displays potent cell killing in the context of key resistance mutations • We have shown that BTK degradation translates into clinical responses across key mutati
Slide 6: Blockbuster Opportunity in BTK Market
Blockbuster Opportunity in BTK Market $8.7 billion in annual sales of approved BTK inhibitors 6 • Next generation BTK inhibitors are currently taking market share from Imbruvica • All BTK inhibitors share resistance mutation vulnerabilities • Opportunity for Nurix BTK degraders to displace both cova
Slide 7: Highly selective BTK degrader NX-5948
Highly selective BTK degrader NX-5948 7
Slide 8: 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 [fully enrolled] Ongoing CLL Phase 1b expansion cohorts 50 mg QD 100 mg QD 200 mg QD 300 mg QD 450 mg QD 600 mg QDNHL/WM (up to 66 patients) CLL/SLL (200mg) Prior BTKi and BCL2i
Slide 9: 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 10: 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 11: NX-5948 Efficacy: Clinical Response
NX-5948 Efficacy: Clinical Response Broad antitumor activity in CLL as demonstrated by significant lymph node reduction and ORR 11Data cutoff: 17 April 2024SPD, sum of products diameters; CR, complete response; CRi, complete response with incomplete marrow recovery; PR, partial response; nPR, nodula
Slide 12: NX-5948 Efficacy: Duration of Treatment
12 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 13: Case Study 1: 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 13 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 1: Patient with CLL and CNS Involvement Deepening response over time appr
Slide 14: Case Study 2: 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 15: Case Study 2: CLL Patient with Extensive Prior Treatment
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 15Data cutoff: 31 May 2024 Case Study 2: 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 16: Mutation Status and BTK Degradation
Mutation Status and BTK Degradation NX-5948 induces rapid and robust degradation of wild-type and mutant BTK 16 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 17: Clinical Activity in Patients with Baseline Mutations
17 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 18: Clinical Activity in Patients with Baseline Mutations
18 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 19: Accelerating Development of NX-5948 with First Pivotal Study in 2025
Nurix Is Accelerating Development of NX-5948 with First Pivotal Study To Be Initiated in 2025 CLL: Clear demonstration of clinical activity in difficult to treat populations • Phase 1a enrollment complete with ~70% ORR as of April 17, 2024 data cutoff (announced at EHA 2024) • Enrolling Phase 1b i
Slide 20: Significant Opportunity in CLL Across Lines of Treatment
20 Significant Opportunity in CLL Across Lines of Treatment ~11,400 pts ~7,600 pts* ~19,200 pts Post-BTKi / post-BCL2i (Fast Track) Label expansion opportunities 3L+ CLL NX-5948 monotherapy 2L CLL NX-5948 monotherapy 1L CLL NX-5948 monotherapy NX-5948 + Ven Pivotal trials in r/r CLL Monotherapy post
Slide 21: NX-2127: Dual acting BTK/IKZF degrader
Dual acting BTK/IKZF degrader with immunomodulatory activity NX-2127 21IKZF: Ikaros zinc finger family of transcription factors
Slide 22: NX-2127 Phase 1a/1b Trial Design
Oral daily dosing Phase 1a Accelerated titration / 3+3 escalation (n∼60a) CLL/SLL, MCL, DLBCL, FL, MZL, WM Phase 1b Select cohort expansionb CLL/SLL (100 mg) (n=40) MCL (300 mg) (n=20) DLBCL, WM (300 mg) (n=20)50 mg 100 mg 200 mg 300 mg CLL, chronic lymphocytic leukemia; DLBCL, diffuse large B-cell
Slide 23: Ongoing Durable Complete Responses in DLBCL and MCL
Ongoing Durable Complete Responses With Over One Year of Follow Up Seen in DLBCL and MCL 23BTKi, Bruton’s tyrosine kinase inhibitor; CR, complete response; DLBCL, diffuse large B-cell lymphoma; FL, follicular lymphoma; MCL, mantle cell lymphoma; MZL, marginal zone lymphoma; PD, progressive disease;
Slide 24: Rapid and Sustained Complete Response in R/R DLBCL With NX-2127
Rapid and Sustained Complete Response in Relapsed/Refractory DLBCL With NX-2127 24 Confirmatory Week 16 Scan Deauville score: 2 Baseline FDG-PET CT Scan Disease Assessment Deauville score: 5 Bladder Bladder • 84-year-old woman with multiply relapsed ABC- DLBCL following 4 lines of aggressive therapy
Slide 25: Rapid and Sustained Complete Response in R/R MCL With NX-2127
Rapid and Sustained Complete Response in Relapsed/Refractory MCL With NX-2127 25 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 stem cell transplant, chemo- immunotherapy, and ibr
Slide 26: Near-Term Next Steps for NX-2127
Near-Term Next Steps: Introduce New Commercial Form of NX-2127 and Reinitiate Phase 1b Enrollment for Aggressive NHL Phase 1a Anticipated Phase 1b Expansion Cohorts Dose escalation prioritizes MCL DLBCL 3+3 standard design DLBCL 26 MCL
Slide 27: NX-1607: Oral CBL-B Inhibitor for Immune Oncology
Oral CBL-B Inhibitor for Immune Oncology Indications NX-1607 27 CBL-B TumorDCDying tumor Lymph node T cell Blood Tumor Dying tumor T cell NK cell CBL-B inhibition promotes the activation of T cells, NK cells, dendritic cells CBL-B: Casitas B lymphoma-b
Slide 28: NX-1607 Mechanism of Action: Intramolecular Glue
NX-1607 Mechanism of Action: Intramolecular Glue TKB RING Y363 Closed State INACTIVE TKB Y363 E2 TKB pY363 E2 Substrate protein 1. Kinase Phosphorylation locks CBL-B in the ACTIVE Conformation p 2. E2/substrate NX-1607 acts as an intramolecular glue forcing CBL-B in its folded INACTIVE state TKB RIN
Slide 29: Single-Agent NX-1607 Induces Antitumor Response in Multiple Models
29 Single-Agent NX-1607 Induces Antitumor Response in Multiple Models NX-1607 Prolonged Survival NX-1607 Reduced Tumor Volume NX-1607 Reduced Tumor Volume NX-1607 30 mg/kg day 7 to 46 NX-1607 30 mg/kg day 16 to 28 Colorectal Triple-Negative Breast B Cell Lymphoma Shaded area indicates dosing period
Slide 30: NX-1607 and Anti-PD-1 Synergize in Multiple Tumor Models
NX-1607 and Anti-PD-1 Synergize to Enhance Anti-Tumor Effects and Survival of Mice in Multiple Tumor Models Colorectal (CT26) Triple-Negative Breast (4T1) Shaded area indicates dosing period: NX-1607 (30 mg/kg, PO daily) and anti-PD-1 twice a week at 10 mg/kg dosing period Colorectal (MC38) 30 Vehic
Slide 31: NX-1607-101: Phase 1 First-in-Human Trial Design
NX-1607-101: Phase 1 First-in-Human Clinical Trial Design 31 MTD or RP1bD(s) Phase 1a dose escalation Phase 1b potential expansion indications HNSCC Advanced NSCLC Recurrent melanoma Platinum-resistant EOC Advanced gastric/GEJ cancer mCRPC Arm 1 NX-1607 monotherapy dose escalation Arm 2a NX-1607 dos
Slide 32: Defining Success in 2024
32 NX-5948 NX-1607 Research pipeline Note: All anticipated timing is based on calendar-year periods Present updated Phase 1a clinical data supporting Phase 1b dose expansion • Accelerate Phase 1 enrollment to enable pivotal trials • Complete IND-enabling studies for autoimmune indications • Presen
Slide 33: Pipeline of Proprietary and Partnered Programs in Oncology and I&I
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 34: Degrader-Antibody Conjugates (DACs) and Seagen Deal Terms
Advancing a New Therapeutic Class Degrader-Antibody Conjugates (DACs) 34 • DACs combine the catalytic activity of a Targeted Protein Degrader (TPD) with the specificity of an antibody • DACs represent the next generation of antibody drug conjugates (ADCs) • $60 million upfront cash payment • $3.4 bi
Slide 35: Industry Leading DELigase Platform for TPD Drug Discovery
0 2 4 6 0 .0 0 0 0 1 0 .0 0 0 1 0 .0 0 1 0 .0 1 0 .1 1 M e a n U n b o u n d D ru g C o n c e n tra tio n in P la s m a T im e (h ) Fr ee D ru g C on ce n tr at io n (u M ) Industry Leading DELigase Platform for TPD Drug Discovery Direct-to-Cell Biology HT Screening for in vivo exposure 35 Ligase En
Slide 36: Strong Financial Position
Strong Financial Position $452.5 million in cash and investments as of May 31, 2024 R&D collaboration cashflow: • Gilead: $45M upfront and $85M in fees and milestone payments earned to date • Sanofi: $55M upfront, $22M in expansion option exercise, and $13M in milestone payments earned to date • Sea
Slide 37: Thank you
Thank you
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