Nurix Therapeutics, Inc. · NASDAQ:NRIX
Nurix Therapeutics — Investor Presentation (January 2023)
35 slides from Nurix Therapeutics's investor presentation, Jan 9, 2023
Slide 1: Leader in Targeted Protein Modulation: Investor Presentation January 2023
Exhibit 99.1 Leader in Targeted Protein Modulation Nurix Therapeutics Blazing a New Path in Medicine Investor Presentation January 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: 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 Targeted Protein Ubiquitin is ligate
Slide 4: 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 ü Advanced to Ph 1b in CLL NX-2127 BTK-IKZF B-cell malignanciesü Efficacy established in CLL Or
Slide 5: Significant Advancement of the Collaboration Pipeline during 2022
Significant Advancement of the Collaboration Pipeline during 2022, Including Targets Considered Undruggable Ligand Degrader Cellular In vivo Oral DC Discovery Discovery Profiling Profiling exposure nomination Target 1 Target 2 Target 3 Target 4 Druggable Targets Target 5 Difficult-to-Drug Targets Ta
Slide 6: 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 • Positive clinical activity in CLL patients, • Clinical evidence of potent BTK including responses in patients with degradation in all patients tested BTK or BCL2 mutati
Slide 7: Nurix BTK Degrader Franchise: Two BTK Degraders for B-cell Malignancies
Nurix BTK Degrader Franchise: Two BTK Degraders to Cover the Landscape of B-cell Malignancies Established Targets Immuno- BTK modulatory (e.g., Ibrutinib-$7B) Both (e.g., lenalidomide-$13B) NX-2127 for B-CELL MALIGNANCIES ANNUAL INCIDENCE (US & EU) BTK inhibitor resistance in Chronic Lymphocytic Leu
Slide 8: Resistance to Noncovalent BTK Inhibitors Presents a New Challenge
Resistance to Noncovalent BTK Inhibitors Presents a New and Growing Challenge to Treatment “Our data suggest potential new therapeutic approaches to overcome the newly described BTK inhibitor resistance mechanisms. For example, these data provide a rationale for therapies aimed at addressing the pot
Slide 9: Nurix Degraders Address Emerging Resistance Mutations and BTK Scaffolding
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
Slide 10: 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 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 post treatment with pirtobrut
Slide 11: NX-2127 is a Dual Acting Agent Degrading 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
Slide 12: NX-2127-001: Trial Design
NX-2127-001: Trial Design Phase 1 trial in adults with relapsed/refractory B-cell malignancies Dose escalation Dose expansion options • CLL Phase 1b expansion cohort ongoing at 100 mg dose Objectives: − MTD not established CLL failed 2 or more prior treatments including a BTK inhibitor and • Assess
Slide 13: Baseline Characteristics
Baseline Characteristics Elderly population with multiple prior lines of targeted therapies and acquired mutations CLL Overall population Characteristics (n=23) (N=36) Median age, years (range) 75 (61–90) 75 (50–92) Female, n (%) 9 (39.1) 13 (36.1) Male, n (%) 14 (60.9) 23 (63.9) Lines of prior ther
Slide 14: NX-2127 Leads to Robust BTK Degradation and Decrease in B-cell Activation
NX-2127 plasma trough concentration (ng/mL) NX-2127 Leads to Robust BTK Degradation and Decrease in B-cell Activation Circulating plasma CCL4 Patients with CLL (100 mg) 30 5000 in patients with CLL (100 mg) 30000 3750 20 CCL4 measured in 25000 patient plasma with an 2500 ELISA-based assay 20000 HMPC
Slide 15: NX-2127 Preliminary Efficacy: Positive Initial Findings in CLL
NX-2127 Preliminary Efficacy Positive Initial Findings in CLL Two or more prior treatments including: 100 Disease-evaluable patients n=15 BTKi BTKi and BCL2i (‘Double exposed’) a Objective response rate, % (95% CI) 33 (12–62) 50 BTK mutation at baseline * Best response, n (%) Treatment ongoing CR 0
Slide 16: First Demonstration of Clinical Activity of a Degrader Against BTK Mutations
First Demonstration of Clinical Activity of a Degrader Against a Range of BTK Mutations NX-2127 Preliminary Efficacy in Patients with CLL BTK degradation in CLL patients Disease-evaluable patients 100 with known BTK mutation status BTK WT 6000 BTK Kinase Dead BTK WT; n=11 50 5000 BTK Kinase Dead (C4
Slide 17: Two Heavily Pre-Treated Patients with Non-GCB DLBCL
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)
Slide 18: Rapid BTK Degradation and Confirmed Complete Response Following NX-2127
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
Slide 19: NX-2127: Early Signs of Meaningful Clinical Activity in CLL and NHL
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
Slide 20: NX-5948-301: Trial Design
NX-5948-301: Trial Design Phase 1 trial in adults with relapsed/refractory B-cell malignancies Dose escalation Dose expansion options • Phase 1a dose escalation is ongoing at clinical sites in the U.K. Objectives: CLL/SLL without C481 mutation (up to 20) • Assess safety and tolerability • Plans to i
Slide 21: First Report of BTK Degradation with NX-5948
First Report of BTK Degradation with NX-5948 in Patients with B Cell Malignancies Initial proof of mechanism • Rapid and sustained Patien t 1 (50mg) 15000 degradation of BTK Patien t 2 (50mg) 12500 Patien t 3 (50mg) • Robust BTK Patient 4 (50mg) degradation observed 10000 Patien t 5 (100mg) in all p
Slide 22: Targeting CBL-B Enhances Antitumor Response
Targeting CBL-B Enhances Antitumor Response A Master Orchestrator of the Immune System CBL-B mediated mechanisms strongly restrains a productive anti-tumor response Lymph node T cell CBL-B Blood CBL-B inhibition increases: Tumor • DC and NK infiltration and function Dying Tumor DC tumor • T cell pri
Slide 23: NX-1607 Mechanism of Action: Intramolecular Glue
NX-1607 Mechanism of Action: Intramolecular Glue Substrate protein E2 E2 Y363 p NX-1607 Y363 pY363 1. Kinase RING RING TKB TKB TKB TKB 2. E2/substrate NX-1607 acts as an Closed State Opened State Phosphorylation locks intramolecular glue INACTIVE CBL-B in the ACTIVE forcing CBL-B in its Conformation
Slide 24: NX-1607 Increases IL-2 and IFN-γ Secretion in T Cells
NX-1607 Increases IL-2 and IFN-���� Secretion in TCR Stimulated Primary Human T cells IL-2 Anti-CD3 IL-2 Anti-CD3/CD28 NX-1607 increases TCR stimulation-dependent production of IL-2 and IFN-���� in primary human T cells IFN-���� Anti-CD3 IFN-���� Anti-CD3/CD28 NX-1607 has no impact in the absence of
Slide 25: Single-Agent NX-1607 Induces Antitumor Response in Multiple Models
Single-Agent NX-1607 Induces Antitumor Response in Multiple Models NX-1607 NX-1607 NX-1607 Reduced Tumor Volume Prolonged Survival Reduced Tumor Volume Colorectal Triple-Negative Breast B Cell Lymphoma Vehicle 1400 100 Vehicle NX-1607 1200 NX-1607 75 1000 <0.0001 p= 800 50 600 p<0.0001 400 25 200 0
Slide 26: 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) Colorectal (MC38) Triple-Negative Breast (4T1) Day 28 4T1 Lung Metastases p<0.01 15000 p<0.01 10000 5000 200 100 0 Vehicle NX-1607 anti-PD-1 NX-1607+anti-PD-1 Shaded area ind
Slide 27: NX-1607-101: Phase 1 Clinical Trial Design
NX-1607-101: Phase 1 first-in-human clinical trial design Two-Part Phase 1 Monotherapy Trial of NX-1607 in Relapsed or Refractory Tumors Cohort Expansion Dose Escalation Objectives: Melanoma • Assess safety and tolerability Squamous Cell Carcinoma of the • Identify maximum tolerated dose Head and Ne
Slide 28: UbiScan Identified Direct CBL Substrates Within TCR Signaling Cascade
UbiScan Identified Direct CBL Substrates Within the T Cell Receptor (TCR) Signaling Cascade Decreased signal represents direct substrates ubiquitinated by CBL-B ligase activity Inhibiting CBL-B decreases ubiquitination of important T Cell receptor signaling molecules 28
Slide 29: Phospho-Protein Flow Cytometry Assay Identified Proximal Biomarkers
Phospho-Protein Flow Cytometry Assay Identified P roximal Biomarkers Phosphorylation of proximal biomarkers in CD8+ T cells • Stimulated human PBMCs with or without CBL-B inhibition • Cells were stained with a panel of phospho-specific antibodies for proteins downstream the TCR signaling • Express
Slide 30: Dose Dependent Increases of CBL-B Proximal Biomarker Correlate with Antitumor Effects
Dose Dependent Increases of CBL-B Proximal Biomarker Correlates with Antitumor Effects of NX-1607 Pharmacodynamic relationship in mice following NX-1607 dosing 100 80 60 Efficacious 40 Range 20 0 0.1 1 10 100 NX-1607 (mg/kg) In vivo efficacy observed between 10-60 mpk which corresponds to ~20-60% pH
Slide 31: Novel Biomarker and First Evidence of Target Engagement for a CBL-B Inhibitor
Characterization of a Novel Biomarker and First Evidence of Target Engagement for a CBL-B Inhibitor in the Clinic Human whole blood and dose projection modeling Clinical data Maximal % pHS1+ expressing CD8+ T cells observed in C1D1 31
Slide 32: CBL-B Inhibition as Centerpiece of Immuno-Oncology Therapy
CBL-B Inhibition Has the Potential To Be the Small Molecule Centerpiece of Immuno-Oncology Therapy Post-ICI (Melanoma, NSCLC, Prostate, MSS Colorectal Ovarian, Gastric DLBCL (including Richter’s) TNBC, Meso, Urothelial, etc) Low-Immunogenicity Tumors Suppressive TME Acquired Resistance T-Cell Dysfun
Slide 33: Defining Success in 2023
Defining Success in 2023 B-cell malignancies Immune oncology Platform & pipeline Research NX-5948 NX-1607 NX-2127 pipeline • Present initial clinical • Present initial clinical • Select new targeted • Present updated data from Phase 1a data from Phase 1a protein degrader Phase 1 clinical data in H2
Slide 34: Strong Financial Position
Strong Financial Position $414M in cash and investments as of August 31, 2022 R&D collaboration details: • Funded through key readouts for all clinical programs • Gilead $45M upfront and up to $2.3B in development, regulatory • Cash runway into Q4 2024 excluding any future potential and sales milest
Slide 35: Thank you
Thank you
Nurix Therapeutics — Investor Presentation (January 2023) on 6ix