Nurix Therapeutics, Inc. · NASDAQ:NRIX
Nurix Therapeutics — Investor Presentation (January 2024)
44 slides from Nurix Therapeutics's investor presentation, Jan 8, 2024
Slide 1: Leader in Targeted Protein Modulation: Nurix Therapeutics Investor Presentation
Leader in Targeted Protein Modulation Nurix Therapeutics Blazing a New Path in Medicine Investor Presentation January 2024 Exhibit 99.1
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: Targeted Protein Modulation: TPM = TPD + TPE
Targeted Protein Modulation: TPM = TPD + TPE Nurix Drugs Engage Ligases for the Treatment of Cancer Targeted Protein Degradation (TPD) Ubiquitin is ligated to target proteins to tag them for degradation by the proteasome Inhibit ligases to increase specific protein levels Harness ligases to decrease
Slide 4: Major Accomplishments by Nurix in 2023
• Led the field of BTK degraders demonstrating clinical efficacy across B-cell malignancies with the potential to displace BTK inhibitors by addressing drug resistance and scaffolding effects • Expanded therapeutic focus into inflammation & immunology with IRAK4 degrader licensed by Gilead and plans
Slide 5: 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-2127 BTK-IKZF B-cell malignancies NX-5948 BTK B-cell malignancies TPE NX-1607 CBL-B Immuno-Oncology TPD Multiple Undisclosed Undisclosed Multiple Undisclosed Undisclosed Multiple Undisclosed Undisc
Slide 6: Advancing a New Therapeutic Class: Degrader-Antibody Conjugates (DACs)
Advancing a New Therapeutic Class Degrader-Antibody Conjugates (DACs) 6 • 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 bil
Slide 7: Targeted Protein Degradation
7 Targeted Protein Degradation Harnessing the ubiquitin proteosome system to eliminate disease proteins Ubiquitin BTK Ubiquitination of Protein BTK Destroyed by the Proteasome Degrader recycling Cereblon E3 Ligase Complex BTK Poly Ubiquitinated Proteins E2 Nurix degrader drugs BTK NX-5948 MOA
Slide 8: A First-In-Class Franchise of BTK Degraders
A First-In-Class Franchise of BTK Degraders NX-5948 & NX-2127 – The big picture 8 BTK degraders can overcome treatment emergent resistance mutations BTK degraders have the potential to displace inhibitors BTK degraders may expand the market in other B-cell malignancies and autoimmune diseases NX-594
Slide 9: Blockbuster Opportunity in BTK Market
Blockbuster Opportunity in BTK Market $8.4 billion in annual sales 9 • 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 covalent and non- covalent inhi
Slide 10: Evolution of BTK Targeted Therapies: Resistance Is Futile
1st Generation Covalent inhibitor Non-Covalent Inhibitors Next Generation Covalent inhibitors Degraders Evolution of BTK Targeted Therapies Resistance Is Futile Ibrutinib Zanubrutinib Acalabrutinib Pirtobrutinib NX-5948 NX-2127 10 Inhibitors share common resistance mutations
Slide 11: BTK Degraders Disrupt BCR Signaling By Removal of the Protein
Nurix Degraders: 1) Eliminate the scaffolding function of BTK oncogenic signals 2) Are effective against resistance mutations through binding cooperativity between BTK and the ligase complex 11 BTK Degraders Disrupt BCR Signaling By Removal of the Protein and All of Its Functions Removal of BTK disr
Slide 12: NX-5948 Is More Potent and Broadly Active Than All BTK Inhibitors Tested
12 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 mutation
Slide 13: Nurix BTK Degrader Franchise: Two BTK Degraders to Cover B-Cell Malignancies
B-Cell Malignancies Annual Incidence (U.S. & EU) Nurix BTK Degrader Franchise: Two BTK Degraders to Cover the Landscape of B-Cell Malignancies BTK, Bruton tyrosine kinase; DLBCL, Diffuse large B cell lymphoma; CLL, Chronic lymphocytic leukemia; MCL, Mantle cell lymphoma; WM, Waldenstrom's macroglobu
Slide 14: NX-5948-301: Trial Design
NX-5948-301: Trial Design Phase 1a/b trial in adults with relapsed/refractory B-cell malignancies aSubtypes include: transformed indolent lymphoma (e.g., grade 3b/transformed FL), Richter-transformed DLBCL, high-grade B-cell lymphoma with MYC and BCL-2 and/or BCL-6 rearrangements, high-grade B-cell
Slide 15: Baseline Demographics and Disease Characteristics
Baseline Demographics and Disease Characteristics Heavily pretreated population Characteristics Patients with CLL (n=7) Patients with NHL/WM (n=19) Overall population (N=26) Median age, years (range) 64.0 (53–75) 63.0 (42–79) 63.5 (42–79) Male, n (%) Female, n (%) 5 (71.4) 2 (28.6) 13 (68.4) 6 (31.6
Slide 16: NX-5948 Was Well Tolerated
• No atrial fibrillation/flutter or hypertension • No DLTs and no TEAEs resulting in drug discontinuation • Four NX-5948-related grade ≥3 TEAEs (3 neutropenia, 1 thrombocytopenia); no related serious adverse events aPurpura/contusion includes episodes of contusion or purpura; bAggregate of ‘thromboc
Slide 17: 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 TEAEs, n (%) 50 mg (n=7) 100 mg (n=6) 200 mg (n=6) 300 mg (n=4) 450 mg (n=3) All doses (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 18: NX-5948 Treatment Results in Rapid, Robust and Sustained BTK Degradation
NX-5948 Treatment Results in Rapid, Robust and Sustained BTK Degradation Dose Number of patients per day (mg) Day 1 Day 2 Day 8 Day 15 Day 22 Day 29 50 7 7 7 6 5 6 100 6 6 5 6 6 5 200 6 6 6 6 4 3 300 4 4 4 4 4 2 BTK, Bruton’s tyrosine kinase; MFI, mean fluorescence intensity;
Slide 19: Broad Antitumor Activity in CLL
Broad Antitumor Activity in CLL as Demonstrated by Significant Lymph Node Reduction and Objective Response Rate 19 • 6/7 patients showed clinical benefit (3 PRs all ongoing, 3 SD with 2 ongoing) • All patients had evidence of lymph node reduction CLL disease-evaluable patientsa n=7 Objective respons
Slide 20: Responses Are Durable and Treatment Ongoing in Patients with CLL
Responses Are Durable and Treatment Ongoing in Patients with CLL Data cutoff: 17 Oct 2023 20 CLL, chronic lymphocytic leukemia NX-5948: Time on study for patients with CLL * * Patient enrolled with CLL subsequently confirmed to have Richter’s transformation to Hodgkin's disease
Slide 21: Responses to NX-5948 Observed Across NHL Subtypes
0 20 40 60 80 260 -80 -60 -40 -20 M ax im um P er ce nt C ha ng e fro m B as el in e in S um o f P ro du ct D ia m et er s Assigned Dose (mg)Treatment Ongoing 50 100 200 300 MCL DLBCL PCNSL MCL MCL MZL DLBCL FL MCL MZL DLBCL Responses to NX-5948 Observed Across NHL Subtypes NHL/WM disease-evaluable
Slide 22: Durable Responses in Patients with NHL
Durable Responses in Patients with NHL Data cutoff: 17 Oct 2023 22 NX-5948: Time on study for patients with NHL DLBCL, diffuse large B cell lymphoma; FL, Follicular lymphoma; MCL, Mantle cell lymphoma; MZL, Marginal zone lymphoma; NHL, non- Hodgkin’s lymphoma; PCNSL, primary CNS lymphoma; PD, progre
Slide 23: Vision: Prioritizing NX-5948 in CLL and Enabling Broad Strategy in NHL
23 Vision: Prioritizing NX-5948 in CLL and Enabling Broad Strategy in NHL • Accelerating enrollment in dose escalation to identify Phase 1b expansion dose levels for CLL and NHL with expansion planned for early 2024 Enable potential accelerated approval(s) in r/r CLL/MCL/WM Enable combinations for e
Slide 24: Beyond Hem/Onc: NX-5948 in Inflammation & Immunology Models
24 Beyond Hem/Onc: NX-5948 Is Highly Effective in Models of Major Inflammation & Immunology Indications 0 5 10 15 0 1 2 3 4 Rheumatoid Arthritis Model Days C lin ic al A rth rit is S co re * *** ******** Tx *p<0.05, **p < 0.01, ***, p < 0.001, ****p < 0.0001 compared to vehicle control Source: Rount
Slide 25: NX-2127-001 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 26: Baseline Demographics and Disease Characteristics
Baseline Demographics and Disease Characteristics Heavily pretreated population with significant acquired resistance mutations Characteristic CLL/SLL (n=33) NHL/WM (n=21) Overall population (N=54) Median age, years (range) 74.0 (58.0–90.0) 70.0 (50.0–92.0) 72.5 (50.0–92.0) Female, n (%) Male, n (%)
Slide 27: Baseline Demographics and Disease Characteristics (Cont'd)
Baseline Demographics and Disease Characteristics (Cont’d) Heavily pretreated population with significant acquired resistance mutations aPatients could have multiple BTK mutations; mutations were tested centrally at baseline by next-generation sequencing (allelic frequency ≥5% is reported) bL845F, D
Slide 28: 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) aAggregate of ‘neutropenia’ and ‘neutrophil count decreased’; bBruising/contusion includes episodes coded as contusion; cAggregate of ‘thrombocy
Slide 29: NX-2127 Rapid, Robust and Sustained BTK Degradation With Ikaros Degradation
B) BTKa degradation in patients receiving NX-2127A) NX-2127 C1D1 pharmacokinetics C) Ikarosb degradation in patients receiving NX-2127 NX-2127 Treatment Results in Rapid, Robust and Sustained BTK Degradation With Clinically Relevant Ikaros Degradation Dose (mg) Number of patients per day Day 0 Day 2
Slide 30: Broad Antitumor Activity in CLL/SLL
Broad Antitumor Activity in CLL/SLL as Demonstrated by Significant Lymph Node Reduction and Objective Response Rate CI, confidence interval; CLL, chronic lymphocytic leukemia; CR, complete response; PD, progressive disease; PR, partial response; SD, stable disease; SLL, small lymphocytic leukemia; S
Slide 31: Durable Responses Seen in Heavily Pretreated CLL/SLL Patients
Durable Responses Seen in Heavily Pretreated CLL/SLL Patients 31 NX-2127 Time on study for CLL/SLL subjects * * * * * * * ** * * *□ BTK Mutation Treatment Ongoing Patient with SLL * □ Assigned Dose (mg) Response 100 150 200 300 PR PR-L SD PD NX-2127: Time on study for patients with CLL/SLL 0 1 2 3 4
Slide 32: Responses Observed Across NHL Subtypes Including Complete Responses
Responses Observed Across NHL Subtypes Including Rapid and Sustained Complete Responses CR, complete response; DLBCL, diffuse large B-cell lymphoma; FL, follicular lymphoma; MCL, mantle cell lymphoma; MZL, marginal zone lymphoma; NHL, non-Hodgkin’s lymphoma; PD, progressive disease; PR, partial resp
Slide 33: Ongoing Durable Complete Responses in DLBCL and MCL
Ongoing Durable Complete Responses With Over One Year of Follow Up Seen in DLBCL and MCL 33BTKi, 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 34: Rapid and Sustained Complete Response in Relapsed/Refractory DLBCL
Rapid and Sustained Complete Response in Relapsed/Refractory DLBCL With NX-2127 34 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 35: Rapid and Sustained Complete Response in Relapsed/Refractory MCL
Rapid and Sustained Complete Response in Relapsed/Refractory MCL With NX-2127 35 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 36: Vision: Focused Strategy With NX-2127 in NHL
36 Vision: Focused Strategy With NX-2127 in NHL Initiation of advanced development activities are dependent on threshold activity in Phase 1b and emerging data for NX-5948 Establish ORR and CR rate in DLBCL and MCL Enable combinations for earlier line trials r/r DLBCL Potential monotherapy 1L DLBCL
Slide 37: Targeting CBL-B Enhances Antitumor Response
Targeting CBL-B Enhances Antitumor Response A Master Orchestrator of the Immune System 37 CBL-B TumorDCDying tumor Lymph node T cell Blood Tumor Dying tumor T cell NK cell CBL-B inhibition increases: • DC and NK infiltration and function • T cell priming • Cytotoxic T cells function • Ability of T c
Slide 38: 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 39: Single-Agent NX-1607 Induces Antitumor Response in Multiple Models
39 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 40: 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) 40 Vehic
Slide 41: NX-1607-101: Phase 1 First-in-Human Clinical Trial Design
NX-1607-101: Phase 1 First-in-Human Clinical Trial Design Phase 1 trial testing both monotherapy and combination with paclitaxel in relapsed or refractory tumors Dose Escalation Potential Cohort Expansion Melanoma Platinum Resistant Epithelial Ovarian Cancer (EOC) Gastric Cancer Squamous Cell Carcin
Slide 42: Defining Success in 2024
42 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 43: Strong Financial Position
Strong Financial Position $329M includes funds as of August 31, 2023, and $60M from Pfizer deal R&D collaboration cashflow: • Gilead: $45M upfront and $67M in licensing fee and milestone payments earned to date • Sanofi: $77M upfront and $7M in milestone payments earned to date • Seagen (now part of
Slide 44: Thank you
Thank you
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