Nurix Therapeutics, Inc. · NASDAQ:NRIX

Nurix Therapeutics — 5th Annual TPD Summit (October 2022)

25 slides from Nurix Therapeutics's conference presentation, Oct 26, 2022

  1. Slide 1: Leader in Targeted Protein Modulation: The First BTK Degraders in Hematologic Malignancies

    Exhibit 99.1 Leader in Targeted Protein Modulation The First BTK Degraders in Hematologic Malignancies: The Latest from the Clinic Arthur T. Sands, M.D., Ph.D. President & CEO 5th Annual TPD Summit Boston, MA October 26th, 2022 1

  2. 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

  3. Slide 3: Nurix Drugs Engage Ligases for the Treatment of Cancer

    Nurix Drugs Engage Ligases for the Treatment of Cancer Targeted Protein Modulation: TPM = TPD + TPE A Powerful Targeted protein Cellular System elevation (TPE) Harness ligases to decrease specific protein levels Inhibit ligases to increase specific protein levels Ubiquitin is ligated to Targeted pro

  4. Slide 4: Nurix Is Advancing Four Wholly Owned Clinical Programs with a Deep Pipeline

    Nurix Is Advancing Four Wholly Owned Clinical Programs with a Deep Pipeline of Proprietary and Partnered Novel Targets MOA Drug program Target/delivery Therapeutic area Preclinical Phase 1 Phase 2 Phase 3 NX-2127 BTK-IKZF B-cell malignancies Oral Degrader TPD NX-5948 BTK B-cell malignancies Oral Deg

  5. Slide 5: A First-in-Class Franchise of BTK Degraders: NX-2127 & NX-5948

    A First-in-Class Franchise of BTK Degraders: NX-2127 & NX-5948 NX-2127 NX-5948 BTK DEGRADATION BTK DEGRADATION & IMMUNOMODULATION • Active against multiple BTK inhibitor- • Active against multiple BTK inhibitor- resistant mutations resistant mutations • Robust BTK degradation and • Crosses blood bra

  6. Slide 6: Value Proposition for a BTK Degrader

    Value Proposition for a BTK Degrader Meeting the Unmet Need with NX-2127 Address Dual Overcome scaffolding degrader resistance function activity Activity against Degradation blocks Immunomodulatory resistance mutations to all downstream activity adds second both covalent and non- signaling from BTK

  7. Slide 7: Emerging BTK Mutations Confer Resistance to Covalent and Non-Covalent BTK Inhibitors

    Emerging BTK Mutations Confer Resistance to Covalent and Non-Covalent BTK Inhibitors Pirtobrutinib Ibrutinib resistant resistant V416L L528W M437R C481S A428D T474I Opportunity for BTK degrader? 7 Wang E, et al. NEJM 2022

  8. Slide 8: Nurix Degraders Directly Address Emerging Resistance Mutations and BTK Scaffolding Activity

    Nurix Degraders Directly Address Emerging Resistance Mutations and BTK Scaffolding Activity Many of the mutations that confer resistance Treatment with BTK inhibitors is to BTK inhibitors lack kinase activity changing the resistance landscape C481S 600 T474I WT 400 M437R 200 L528W V416L 0 0 50 100 1

  9. Slide 9: NX-2127 is Active Against Both Wildtype and Mutant BTK

    NX-2127 is Active Against Both Wildtype and Mutant BTK Potential to treat patients who failed both covalent and non-covalent BTK inhibitors BTK degradation in TMD8 cells 125 WT C481S 100 L528W 75 NX-2127 is capable of degrading V416L not only C481S, but also the novel M437R 50 BTK mutations observed

  10. Slide 10: NX-2127 is a Dual Acting Agent That Also Degrades Aiolos

    NX-2127 is a Dual Acting Agent That Also Degrades Immunomodulatory Cereblon Neosubstrate Aiolos Aiolos degradation in T cells • Activity of NX-2127 is pegged to approved agents with well-established efficacy and safety • Dual activity potentially addresses alternative resistance mechanism in CLL • E

  11. Slide 11: BTK Degradation of 80%+ Drives Potent Anti-Tumor Activity in Preclinical Models

    BTK Degradation of 80%+ Drives Potent Anti-Tumor Activity in Preclinical Models BTK degradation in BTK degradation in TMD8 Tumor Growth Peripheral B cells TMD8 Tumor cells 120 120 1400 Vehicle Vehicle Vehicle 100 1200 100 10 mpk 10 mpk 10 mpk NX-2127 30 mpk 30 mpk 1000 30 mpk NX-2127 80 80 90 mpk 90

  12. Slide 12: NX-2127-001 Phase 1a/1b Trial Design

    NX-2127-001 Phase 1a/1b Trial Design Dose escalation Dose expansion options • CLL Phase 1b cohort expansion Objectives: at 100 mg dose CLL failed 2 or more prior treatments • Assess safety and tolerability including a BTK inhibitor and • Identify maximum tolerated dose • 50 mg CLL cohort opened to r

  13. Slide 13: NX-2127-001: Heavily Pre-Treated Patient Population, Including Double-Refractory CLL Patients

    NX-2127-001: Heavily Pre-Treated Patient Population, Including Double-Refractory CLL Patients Overall population CLL Non-CLL Characteristics (n=21)** (n=13) (n=7) Median age, years (range) 76.0 (61–92) 76 (65–86) 77 (67–92) Female, n (%) 7 (33.3) 7 (53.8) 0 Male, n (%) 14 (66.7) 6 (46.2) 7 (100) Pri

  14. Slide 14: NX-2127-001: Safety Observations By Dose

    NX-2127-001: Safety Observations By Dose (All Patients, Grade ≥3) Adverse Event 100 mg (n=10) 200 mg (n=6) 300 mg (n=3) n (%) n (%) n (%) Preferred Term, Grade ≥3 Neutropenia 1 (10%) 3 (50%) 2 (66.7%) Hypertension 0 (0%) 1 (16.7%) 0 (0%) Additional safety observations: Dyspnea 0 (0%) 1 (16.7%) 0 (0%

  15. Slide 15: NX-2127-001: Rapid and Sustained Degradation of BTK in Patients with CLL

    NX-2127-001: Rapid and Sustained Degradation of BTK in Patients with CLL Therapeutic range Target BTK degradation achieved by Day 15 BTK degradation is sustained (steady state) for all starting BTK levels Data cut April 8, 2022 15

  16. Slide 16: Case Study: Patient #1 (Presented at TPD 2021)

    Case Study: Patient #1 (Presented at TPD 2021) Safety Patient history Disease at study entry 78-year-old male Bone marrow involvement: 85.4% Exposure No dose interruptions or modifications with stage IV CLL Spleen: enlarged (15.7 cm) DLT’s None Nodal lesions: several, largest 4.2 cm SAE’s None Prior

  17. Slide 17: NX-2127-001 Phase 1a: Positive Initial Findings in Heavily Pretreated CLL Patients

    NX-2127-001 Phase 1a: Positive Initial Findings in Heavily Pretreated CLL Patients • Meaningful clinical benefit in CLL patients with a median of 6 prior lines of therapy • Biologic activity including nodal reductions and/or lymphocytosis observed in all patients treated • Responses in patients with

  18. Slide 18: Clinical Update: First Report of NX-2127 in Non-GCB DLBCL Patients

    CASE STUDY Clinical Update First Report of Targeted Protein Degrader NX-2127 Initial experience in non-GCB in Diffuse Large B cell DLBCL patients Lymphoma (DLBCL) Robert Brown, M.D. Executive Vice President Clinical Development Nurix Therapeutics October 26, 2022 18

  19. Slide 19: Non-GCB DLBCL Represents an Important Unmet Medical Need

    Non-GCB DLBCL Represents an Important Unmet Medical Need 1,2 • DLBCL is the most common form of lymphoma, representing ~30% of all NHL diagnoses 1,2,3 • ~24,000 people diagnosed in the United States each year, with ~60% 5-year survival DLBCL treatments are the same for all patients, 4 even though it

  20. Slide 20: Mechanistic Rationale for Dual Degrader in DLBCL

    Mechanistic Rationale for Dual Degrader in DLBCL Hyper-activated BCR (CD79b-mut) and TLR (MyD88-mut) signaling are hallmarks of non-GCB DLBCL: • NX-2127 targets both BCR and TLR signaling through BTK degradation • NX-2127 targets non-BTK dependent TLR signaling through its immunomodulatory activity

  21. Slide 21: Dual Targeting of BTK and Immunomodulatory Activity Has Demonstrated Clinical Activity in Non-GCB DLBCL

    Dual Targeting of BTK and Immunomodulatory Activity Has Demonstrated Clinical Activity in Both Relapsed and First-Line Non-GCB DLBCL Goy A, et al. Blood 2019;134:1024–36 Westin J, et al. J Clin Oncol 2022;Aug 11 (epub ahead of print) 21

  22. Slide 22: Two Heavily Pre-Treated Patients with Non-GCB DLBCL Enrolled in NX-2127 Phase 1

    Two Heavily Pre-Treated Patients with Non-GCB DLBCL Enrolled in NX-2127 Phase 1 Dose-Escalation Patient #1 Patient #2 Non-GCB (ABC subtype) Subtype Non-GCB (ABC subtype) Double-hit, BCL2/BCL6 Dose 100 mg 300 mg Time on Study 3.5 months 5 months and ongoing Priors 4 4 Response(s) Stable Disease (SD)

  23. Slide 23: Rapid BTK Degradation and Confirmed Complete Response Following NX-2127 Therapy

    Rapid BTK Degradation and Confirmed Complete Response Following NX-2127 Therapy FDG-PET CT Scan Disease Assessment Baseline Week 16 % BTK remaining in CD19+ B cells Bladder 100 Bladder Patient #2 300 mg 80 60 40 20 0 0 5 10 15 20 25 30 Day % BTK calculated in PBMC Significant Ikaros and Aiolos degra

  24. Slide 24: NX-2127: First-in-Class BTK Degrader Demonstrates Early Signs of Meaningful Clinical Activity

    NX-2127: First-in-Class BTK Degrader Demonstrates Early Signs of Meaningful Clinical Activity in Both CLL and NHL Chronic lymphocytic leukemia (CLL) • Objective responses observed in CLL patients who failed a median of 6 prior lines of therapy including patients who failed BTK inhibitors and BCL2 in

  25. Slide 25: Thank you

    Thank you 25

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