Arcus Biosciences, Inc. · NYSE:RCUS
Arcus Biosciences — Goldman Sachs 39th Annual Global Healthcare Conference (June 2018)
43 slides from Arcus Biosciences's conference presentation, Jun 12, 2018
Slide 1: Creating Innovative Cancer Immunotherapies by Leveraging Underexploited Biological Opportunities
Creating Innovative Cancer Immunotherapies by Leveraging Underexploited Biological Opportunities June 2018
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 h
Slide 3: Corporate Overview
Corporate Overview Our Portfolio ATP-Adenosine Pathway Programs Antibody Programs Collaborations and Anticipated Milestones
Slide 4: Arcus Mission: Creating Innovative Cancer Immunotherapies
Arcus Mission: Creating Innovative Cancer Immunotherapies by Leveraging Underexploited Biological Opportunities • Focused on scientifically-validated, underexploited immuno-oncology (I-O) pathways – Initial focus on the ATP-adenosine pathway • Four product candidates expected to be in the clinic by
Slide 5: Arcus's Strategy Leverages the Essential Role of Combination Therapies in Immuno-Oncology
Arcus’s Strategy Leverages the Essential Role of Combination Therapies in Immuno-Oncology Our Strategy: • Focus on targets that play a critical role in numerous cancers • Establish broad portfolio of molecules that modulate important immune functions • Design small molecules with highly differentiat
Slide 6: Arcus Leadership Team - Strong Track Record, Individually and as a Team
Arcus Leadership Team - Strong Track Record, Individually and as a Team Terry Rosen, Ph.D. (Founder; CEO) Founder & CEO, Flexus VP Therapeutic Discovery (>550 staff) / Site Head (SF, WA) at Amgen EVP Operations (inc. all Research & Preclin. Dev.) at Tularik Juan Jaen, Ph.D. (Founder; President) Foun
Slide 7: Arcus Has Rapidly Created a Broad Portfolio of Immuno-Oncology Programs
Arcus Has Rapidly Created a Broad Portfolio of Immuno-Oncology Programs Phase 1b Preclinical Phase 1 Combination Status / Milestone Dual and Selective A2R Antagonists AB928 (A2aR/A2bR Antagonist) Phase 1/1b program initiated A003105/A002926 Preclinical characterization ongoing Small Molecule CD73 In
Slide 8: Validated, Highly Efficient Drug Discovery Capability
Validated, Highly Efficient Drug Discovery Capability Four product candidates expected to be in clinical development by YE:2018 (two internally discovered) -- 5th program (arginase) underway 21 months from program initiation to start of Phase 1 2015 2016 2017 2018 April 2015 February December Novemb
Slide 9: Multiple Trial Initiations and Data Readouts Anticipated by H1:2019
Multiple Trial Initiations and Data Readouts Anticipated by H1:2019 H1:18 H2:18 H1:19 AB928 (A2aR/A2bR) HV Study AB928 + AB122 Combo dose escalation, followed by cohort expansions AB928 + Chemo Combo dose escalations, followed by cohort expansions AB122 (anti-PD-1) Single agent dose escalation Singl
Slide 10: Our Portfolio: ATP-Adenosine Pathway Programs
Corporate Overview Our Portfolio ATP-Adenosine Pathway Programs Antibody Programs Collaborations and Anticipated Milestones
Slide 11: ATP-Adenosine Pathway: Highly Promising Pathway in Immuno-Oncology
ATP-Adenosine Pathway: Highly Promising Pathway in Immuno-Oncology Targeting adenosine in cancer immunotherapy: a review of recent progress “…The adenosine pathway is currently viewed as a significant barrier to the effectiveness of immune therapies and becomes an important therapeutic target in can
Slide 12: The ATP-Adenosine Pathway Plays a Critical Role in Immune Suppression
The ATP-Adenosine Pathway Plays a Well Established, Critical Role in Immune Suppression What we know about adenosine: • High levels of adenosine are present in most tumors • Adenosine has a direct impact on T- cell function and activation • T cells cannot become activated in the presence of adenosin
Slide 13: AB928: Highly Differentiated A2R Antagonist
AB928: Highly Differentiated A2R Antagonist • Believed to be the first A2R antagonist in clinical development that has been designed to: Differentiated Approach to A2R – Effectively block the adenosine receptor in the tumor Antagonism microenvironment – Potently inhibit both the A2aR and A2bR recept
Slide 14: AB928 is the Most Potent Antagonist of A2aR Receptors in Whole Blood Assay
AB928 is the Most Potent Antagonist of A2aR Receptors When Tested in a Whole Blood Assay A2aR antagonists currently in clinical development, tested in a whole blood assay in the presence of NECA (conditions that resemble the tumor microenvironment) 1 0 0 Compound IC50 (nM) a In h ib itio n A B 9 2 8
Slide 15: AB928 Also Has Unique Attributes Ideal for the Tumor Microenvironment
AB928 Also Has Unique Attributes Ideal for the Tumor Microenvironment High potency against both the A2aR Ideal pharmacological properties and A2bR receptors allows for for an oncology therapeutic potentially broader activity Compound A2aR (KB, nM)c A2bR (KB, nM)c Attribute AB928 Value Retains potenc
Slide 16: AB928 is Synergistic with anti-PD-L1 and Chemotherapy in Mouse Models
AB928 is Synergistic with anti-PD-L1 and Chemotherapy in Mouse Models MC38 mouse model (in combination AT-3 OVA mouse model (in with anti-PD-L1 antibody) combination with Oxaliplatin) V e h ic le V e h ic le O x (1 0 m g /k g ) 1 0 0 A B 9 2 8 1 2 0 0 O x (5 m g /k g ) ) α -P D -L 1 3 (m m 7 5 A B 9
Slide 17: AB928 Is Synergistic with Doxorubicin in the AT-3 OVA Model
AB928 Is Synergistic with Doxorubicin in the AT-3 OVA Model Samples collected for histopathology **p<0.01 Doxorubicin vs. Doxorubicin + AB928 Similar results observed for the combination of AB928 and doxorubicin in the MCA205 model © 2018 Arcus Biosciences, Inc. 17
Slide 18: AB928 + Doxorubicin Induce Reduced AT-3 Tumor Growth and Histological Changes
AB928 + Doxorubicin Induce Reduced AT-3 Tumor Growth and Significant Histological Changes Example images representing the average tumor mass from each group Vehicle + Dox (53 mg tumor) AB928 + Dox (8 mg tumor) Tum or M ass 125 ** 100 M a s s (m g ) 75 50 25 0 D ox AB 9 2 8 6 m g /k g /D o x Tumors t
Slide 19: AB928 Clinical Program Underway
AB928 Clinical Program Underway • Phase 1 trial in healthy volunteers near completion (n=85, 65 received AB928) – Achieved complete inhibition of pathway at 150mg QD – Half life supports QD dosing – Safe and well tolerated at all doses • Regulatory filings underway to initiate three Phase 1/1b “plat
Slide 20: Data from Phase 1 Trial in HVs: Dose Proportional PK
Data from Phase 1 Trial in HVs: Dose Proportional PK • Dosing completed – MAD cohorts included 10 mg, 25 mg, 75 mg and 150 mg and 200 mg (with food) • No safety issues have been observed • Plasma half-life of approximately 20 hours MAD (day 4) 1 0 0 0 0 (n g /m L ) 1 0 0 0 1 5 0 m g Q D 7 5 m g Q D
Slide 21: AB928 Provided Maximal Inhibition of A2aR Activation on Day 4
AB928 Provided Maximal Inhibition of A2aR Activation on Day 4 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 52 % 53 < 30% 25 mg QD 420 82 % 108 51 % 75 mg QD 1,148 100 % 261 76 % 150 mg QD 2,113 1
Slide 22: AB928 Phase 1/1b Program: Our Approach
AB928 Phase 1/1b Program: Our Approach • Initial Focus on Settings Where Adenosine Pathway is Believed to be Critical, e.g.: – Tumor types characterized by high levels of CD73 expression (NSCLC, CRC, etc.) – Tumor types/settings where the SOC is anti-PD-1 or ICD-inducing chemotherapy • Adaptive Tria
Slide 23: AB928 Phase 1/1b Program: Initial Combination Partners
AB928 Phase 1/1b Program: Initial Combination Partners Focused on combination partners that are currently SOC for specific tumor types AB122 (anti-PD-1) ICD-inducing chemotherapy • A2aR activation induces signaling & • Certain chemotherapies, e.g., transcriptional changes in T cells, oxaliplatin & d
Slide 24: Emerging Clinical Data Supportive of CD73-Adenosine
Emerging Clinical Data Supportive of CD73-Adenosine Molecule Study (Meeting Data (Company) Approach Presented at) Data NIR178 A2aR Data presented on 25 • 2 responses in I-O naïve patients, (Novartis) Antagonist patients with R/R NSCLC including a CR, as monotherapy (ASCO 2018 ) • Doses up to 640 mg
Slide 25: AB928 Phase 1/1b Program: Tumor Type Selection
AB928 Phase 1/1b Program: Tumor Type Selection Evaluating tumor types in which the ATP-adenosine pathway might play an important immunosuppressive role – in three “Tumor-Specific” trials Tumor types High CD73 ICD-inducing expected to be T cell expression chemo is Trial Protocol included infiltration
Slide 26: Phase 1/1b in Breast and Gynecologic Malignancies
1 Phase 1/1b in Breast and Gynecologic Malignancies Expansion cohorts TNBC RP2D of AB928 + AB928 + AB122 AB122 (n=15) Ovarian AB928 + AB122 Expand cohort (n=15) from 15 to 30 Breast and patients based Ovarian Dose escalation of AB928 on achievement (fixed dose for of pre-specified TNBC combination p
Slide 27: Phase 1/1b in Gastrointestinal Malignancies
2 Phase 1/1b in Gastrointestinal Malignancies “Platform” trial design allows us to add new combinations to the protocol, including triple combinations Expansion cohort Gastroesophageal AB928 + AB122 RP2D of AB928 + (n=15) AB122 CRC AB928 + AB122 Expand cohort (n=15) from 15 to 30 Gastro- patients ba
Slide 28: Phase 1/1b in RCC and NSCLC
3 Phase 1/1b in RCC and NSCLC Expansion cohorts NSCLC (PD-1 relapsed) AB928 + AB122 RP2D of AB928 + (n=15) AB122 Expand cohort RCC (PD-1 relapsed) from 15 to 30 AB928 + AB122 patients based Dose escalation of (n=15) on achievement AB928 (fixed dose for of pre-specified combination partner) threshold
Slide 29: AB928 Clinical Biomarker Plan
AB928 Clinical Biomarker Plan Predictive Biomarkers Markers of Immune Activation • CD73 expression • Immunophenotyping (PBMC) − Tumor (IHC & mRNA) • T cell clonality (tumor & PBMC) − Blood (ELISA & Enzym. Assay) − neoE-specific clonal • PD-L1 status expansion • TMB (tumor and/or blood) • T cell acti
Slide 30: AB680: Potentially First Small Molecule CD73 Inhibitor
AB680: Potentially First Small Molecule CD73 Inhibitor • CD73 catalyzes the last step in the conversion of extracellular CD73 Mediates Adenosine ATP to adenosine Production • CD73 inhibition blocks extracellular adenosine production • AB680 is the most advanced small-molecule inhibitor of CD73 • Pot
Slide 31: Structure-Based Design of Extraordinarily Potent CD73 Inhibitors
Structure-Based Design of Extraordinarily Potent CD73 Inhibitors A000934 AB680 hCD73 (CHO cells) IC50 = 0.004 nM IC50 = 26 nM (human T cells) Collaboration with Professor Norbert Sträter (University of Leipzig) © 2018 Arcus Biosciences, Inc. 31
Slide 32: AB680 Potently Inhibits CD73 Enzymatic Activity on CD8+ T Cells
AB680 Potently Inhibits CD73 Enzymatic Activity on CD8+ T Cells Representative data from various separate experiments shown a M E D I9 4 4 7 (C D 7 3 m A b ; P 1 ) 1 0 0 A B 6 8 0 (A rc u s in h ib it o r ) h y d r o ly z e d ] 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
Slide 33: Rationale for a Triple Combination Approach With Anti-PD-1, Anti-TIGIT and CD73 Inhibitor
Rationale for a “Triple Combination Approach” With Anti-PD-1, Anti-TIGIT and CD73 Inhibitor AMP inhibits CD4+ T cell activation (even in the presence of both an anti-PD-1 and anti-TIGIT antibody), an effect that can be reversed by AB680 * ** 3 0 0 0 2 5 0 0 (p g /m l) 2 0 0 0 1 5 0 0 IF N -γ 1 0 0 0
Slide 34: AB680 is Advancing Towards a Phase 1 Trial Initiation Expected in H2:18
AB680 is Advancing Towards a Phase 1 Trial Initiation Expected in H2:18 • Intravenous formulation of AB680 currently in IND-enabling studies – Low clearance, long half-life molecule – Can be administered on the same schedule as AB122 (anti-PD-1) or chemotherapy – Regulatory submission and Phase 1 in
Slide 35: AB122: Anti-PD-1 Antibody with Similar Properties to Approved Agents
AB122: Anti-PD-1 Antibody with Similar Properties to Approved Agents AB122 Has Highly • Fully human antibody with similar binding affinity and other Attractive Properties characteristics to those of pembrolizumab and nivolumab • Full access to AB122 in the US, Europe, Japan and certain other territo
Slide 36: AB154: Differentiated Antibody in a New Immune Checkpoint Class (TIGIT)
AB154: Differentiated Antibody in a New Immune Checkpoint Class (TIGIT) • TIGIT inhibition both reverses immune inhibition and provides tissue-selective immune stimulation Novel Checkpoint Target • Believed to be one of the next potential backbone therapies in I-O • Fully human anti-TIGIT IgG1κ anti
Slide 37: TIGIT Has a Dual Mechanism that Makes this Immuno-Oncology Pathway Unique
TIGIT Has a Dual Mechanism that Makes this Immuno-Oncology Pathway Unique T Cell Tumor Cells NK Cell Myeloid DCs Activation IL-10 Inhibition Red: Suppression Blue: Activation • TIGIT binds to CD155 (high affinity) and CD112 (low affinity) • DNAM-1 competes, with lower affinity than TIGIT, for bindin
Slide 38: ARG-1: Promising Early Stage Program Targeting Myeloid Cells
ARG-1: Promising Early Stage Program Targeting Myeloid Cells Current ARG-1 lead, A003347, has demonstrated highly potent inhibition of human ARG-1 and reversal of ARG-1-mediated repression of T cells Inhibition of human ARG-1 Rescue of ARG-1-mediated repression of CD8+ T cell proliferation A003347 1
Slide 39: Collaborations and Anticipated Milestones
Corporate Overview Our Portfolio ATP-Adenosine Pathway Programs Antibody Programs Collaborations and Anticipated Milestones
Slide 40: Collaboration with Taiho Provides Non-Dilutive Capital
Collaboration with Taiho Provides Non-Dilutive Capital Collaboration Terms: • Taiho acquires an option on Arcus programs for Japan and certain other Asia territories (excluding China) over a A member of the Otsuka Group of 5-year term Companies • $35mm in guaranteed payments over 3 years Pipelin
Slide 41: In-licensing of Anti-PD-1 Antibody Ensures Access
In-licensing of Anti-PD-1 Antibody Ensures Access / Creates Multiple Intra-Portfolio Opportunities Key Terms: • Arcus in-licensed WW rights to AB122 from WuXi (with the exception of China and five other countries outside the US, Established history of working with Europe and Japan) large US and gl
Slide 42: Upcoming Anticipated Milestones
Upcoming Anticipated Milestones Q2:2018 Regulatory filings for dose-escalation trials for first intra-portfolio combinations: AB928 + AB122 and AB928 + Chemo • Final data from healthy volunteer trial for AB928 Q3:2018 • Regulatory filings for AB154 and AB680 • Data from Phase 1 trial of AB122 in p
Slide 43: US BIOS CIE Noe
US BIOS CIE Noe s BIOSCIENCE RCUS
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