Arcus Biosciences, Inc. · NYSE:RCUS
Arcus Biosciences — Investor Presentation (April 2019)
25 slides from Arcus Biosciences's investor presentation, Apr 26, 2019
Slide 1: Creating Innovative Cancer Immunotherapies by Leveraging Underexploited Biological Opportunities
Creating Innovative Cancer Immunotherapies by Leveraging Underexploited Biological Opportunities Corporate Presentation April 26, 2019 NYSE: RCUS
Slide 2: Forward-Looking Statements/Safe Harbor
Forward-Looking Statements/Safe Harbor This presentation contains forward-looking statements about Arcus Biosciences, Inc. (“we,” “Arcus” or the “Company”) made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. All statements other than statements of his
Slide 3: Creating Innovative Cancer Immunotherapies
CREATING INNOVATIVE CANCER IMMUNOTHERAPIES Leverage Underexploited Biological Initial focus on Targets in Promising Pathways ATP-adenosine pathway Four clinical candidates with Broad, Clinical Stage Pipeline multiple data readouts in 2019 Small-molecule discovery engine World-class Drug Discovery En
Slide 4: Our Competitive Advantages
Our Competitive Advantages Best-in-Class Chemistry Portfolio Breadth Translational Medicine AB928 (A2aR/A2bR Antagonist) Stage IIB AB928 + Chemo Advanced solid tumors AB928 + AB122 Advanced solid tumors AB680 (Small Molecule CD73i) AB680 (IV) Phase 1 in HVs AB680 (oral) IND-enabling Stage IV Antibod
Slide 5: Early Clinical Strategy Designed to Support Long Term Success
EARLY CLINICAL STRATEGY DESIGNED TO SUPPORT LONG TERM SUCCESS HEALTHY FLEXIBLE DOSE ESCALATION/ BIOMARKERS VOLUNTEER TRIAL DESIGN EXPANSION “Rapidly identify “Ability to easily “Robust early dataset “Understand therapeutically incorporate and in tumor-specific differences between relevant doses and
Slide 6: Broad Portfolio of Oncology Programs
Broad Portfolio of Oncology Programs Phase 1 Programs* Discovery Preclinical Dose Escalation Dose Expansion AB928 (A2aR/A2bR Antagonist) AB928 + Chemotherapy NSCLC, CRC, GE, TNBC, Ovarian AB928 + AB122 (anti-PD-1) Advanced solid tumors → RCC AB680 (Small Molecule CD73 inhibitor) AB680 (i.v.) Phase 1
Slide 7: Multiple Data Readouts in the Next 12 Months
Multiple Data Readouts in the Next 12 Months 1H:19 2H:19 1H:20 Dose escalation, Cohort expansions AB928 (A2aR/A2bR Antagonist) AB928 + AB122 (anti-PD-1) Dose escalation Cohort expansions AB928 + Chemotherapy Dose escalation Cohort expansions AB680 (Small Molecule CD73 inhibitor) AB680 (CD73) HV Stud
Slide 8: The ATP-Adenosine Pathway Plays a Well Established, Critical Role in Immune Suppression
The ATP-Adenosine Pathway Plays a Well Established, Critical Role in Immune Suppression A2aR Cell death generates extracellular ATP NK Cells Adenosine is generated from ATP ATP by the enzymatic action of CD39 and CD73 A2aR Adenosine binds ATP ATP AMP Adenosine to A2 receptors on immune cells leading
Slide 9: Companies Are Expanding Their CD73-Adenosine Efforts
Companies Are Expanding Their CD73-Adenosine Efforts • A2R antagonist (n=276) • NSCLC, CRPC & CRC • Combinations with PD-L1, abiraterone or enzalutamide • Study expanded multiple times • CD73 + various combinations • Multiple solid tumors (n=310) • mutEGFR NSCLC (n=98) • Pancreatic (n=204) • TNBC (n
Slide 10: AB928 Represents a Potentially Best-in-Class Adenosine Receptor Antagonist
AB928 Represents a Potentially Best-in-Class Adenosine Receptor Antagonist • First A2R antagonist to enter clinical development that: – Was specifically designed for the oncology setting – Inhibits both the A2a and A2b receptors • Multiple advantages over other A2aR antagonists in clinical developme
Slide 11: AB928 Has Unique Attributes Ideal for the Tumor Microenvironment
AB928 Has Unique Attributes Ideal for the Tumor Microenvironment High potency against both the A2aR and Ideal pharmacological properties A2bR receptors allows for potentially for an oncology therapeutic broader activity Compound A2aR (KB, nM)c A2bR (KB, nM)c Attribute AB928 Value Retains potency in
Slide 12: AB928 is the Most Potent Antagonist of A2aR Receptors in a Whole Blood Assay
AB928 is the Most Potent Antagonist of A2aR Receptors When Tested in a Whole Blood Assay A2aR antagonists tested in a whole blood assay in the presence of NECA (conditions that resemble the tumor microenvironment) Compound IC50 (nM) a 1 0 0 In h ib itio n A B 9 2 8 AB928 80 C P I-4 4 4 CPI-444 b ~10
Slide 13: Phase 1 Trial in Healthy Volunteers Demonstrated an Excellent Safety Profile
Phase 1 Trial in Healthy Volunteers Demonstrated an Excellent Safety Profile Design: Multiple Ascending Dose Pharmacokinetics • Double-blinded, randomized, placebo- controlled trial >90% inhibition of A2aR • n=80 randomized 3:1 to AB928 or placebo • Included single ascending dose and multiple ascend
Slide 14: Maximal Inhibition of A2aR Should be Achieved at Doses Between 75-150 mg QD
Based on the HV Data, Maximal Inhibition of A2aR Should be Achieved at Doses Between 75-150 mg QD 2-hr Post-Dose 24-hr Post-Dose AB928 Plasma % Inhibition of AB928 Plasma % Inhibition of Conc. (ng/mL) 5 µM NECA Conc. (ng/mL) 5 µM NECA 10 mg QD 163 51 % 53 (12%)* 25 mg QD 420 82 % 108 51 % 75 mg QD 1
Slide 15: Rationally-Selected Combinations and Settings for Early Clinical Trials
Rationally-Selected Combinations and Settings for Early Clinical Trials Areas of Focus Tumor types selected based on high levels of CD73, extent of T-cell infiltration Combinations with immunogenic cell death (ICD)-inducing chemotherapy Tumor types/settings that are generally non-responsive to anti-
Slide 16: Initial Data for Dose-Escalation Trials by Mid-2019 & Dose Expansion Cohorts in 1H-2020
Initial Data for 3 Dose-Escalation Trials by Mid-2019 & Dose Expansion Cohorts in 1H-2020 Dose Escalation Cohorts Expansion Cohorts Flexible Trial Design (n=12-15 per combination) (n=15-40) AB928 + Doxil® in TNBC • Dose escalation cohorts Initial Data by mid-2019 002 TNBC and Ovarian will assess saf
Slide 17: Extensive Biomarker Plan in Ongoing AB928 Cancer Trials
Extensive Biomarker Plan in Ongoing AB928 Cancer Trials Biomarker Readout Key Objective(s) CD73 status ✓ Determine relationship between CD73 expression (tumor, soluble) and clinical activity Potential predictive • Tumor (IHC & mRNA) ✓ Assess potential of CD73 biomarker as a patient biomarkers • Bloo
Slide 18: AB680: First Small-Molecule CD73 Inhibitor to Enter Clinical Development
AB680: First Small-Molecule CD73 Inhibitor to Enter Clinical Development • CD73 catalyzes the last step in the conversion of extracellular ATP to adenosine • AB680 potentially offers advantages over the anti- CD73 antibodies in development: – Greater inhibition of CD73 enzymatic activity – Deeper tu
Slide 19: AB680 Potently Inhibits CD73 Enzymatic Activity on CD8+ T Cells
AB680 Potently Inhibits CD73 Enzymatic Activity on CD8+ T Cells M E D I9 4 4 7 (C D 7 3 m A b ; P 1 ) a 1 0 0 h y d r o ly z e d ] A B 6 8 0 (A rc u s in h ib it o r ) 7 5 [A M P 5 0 M a x % 2 5 0 -1 3 -1 2 -1 1 -1 0 -9 -8 -7 L o g [A B 6 8 0 ]/(M ) a Molecule synthesized by Arcus based on the follo
Slide 20: Healthy Volunteer Trial for AB680 is Enrolling
Healthy Volunteer (HV) Trial for AB680 is Enrolling Trial Design Key objectives ✓ Single ascending dose design ✓ Determine safety and tolerability ✓ Cohorts (n=8) randomized (3:1) ✓ Assess pharmacokinetics and to AB680 or placebo pharmacodynamics (CD73 inhibition) ✓ Enable initiation of clinical tri
Slide 21: AB122: Anti-PD-1 Antibody with Properties Similar to Those of Approved Agents
AB122: Anti-PD-1 Antibody with Properties Similar to Those of Approved Agents • Fully human antibody with similar binding affinity and other characteristics to pembrolizumab and nivolumab • In-licensed from WuXi, a leading biologics manufacturer – Full development and commercialization rights in the
Slide 22: AB154: The Next Potential I-O Backbone (TIGIT)
AB154: The Next Potential I-O Backbone (TIGIT) Dual Mechanism of Action that Reflects the uniqueness of TIGIT Pathway Blocking TIGIT inhibits an immuno-suppressive pathway while freeing up CD155 to bind to DNAM-1 which is an immune-activating pathway Tumor Cell T Cell/NK Cell T Cell/NK Cell Cytotoxi
Slide 23: Phase 1/1b Dose Escalation Trial of AB154 + AB122
Phase 1/1b Dose Escalation Trial of AB154 + AB122 AB154 + AB122 Key objectives Dose Escalation ✓ Evaluate safety and tolerability AB154 Dose Escalation Cohort 3 ✓ Determine pharmacokinetic and AB154 + pharmacodynamic profile AB122: 240 mg IV Q2W Cohort 4 ✓ Identify RP2D for AB154 as monotherapy and
Slide 24: Active Early Stage Discovery Effort Focused on Small-Molecule Pipeline Expansion
Active Early Stage Discovery Effort Focused on Small- Molecule Pipeline Expansion Arcus is leveraging its small-molecule expertise to continue creating potentially best-in-class and/or first-in-class product candidates Cancer Cell Non-Oncology Intrinsic Applications of Pathways Existing Reversal of
Slide 25: Multiple Data Readouts in the Next 12 Months
Multiple Data Readouts in the Next 12 Months 1H:19 2H:19 1H:20 Dose escalation, Cohort expansions AB928 (A2aR/A2bR Antagonist) AB928 + AB122 (anti-PD-1) Dose escalation Cohort expansions AB928 + Chemotherapy Dose escalation Cohort expansions AB680 (Small Molecule CD73 inhibitor) AB680 (CD73) HV Stud
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