Agenus Inc. · NASDAQ:AGEN
Agenus — Investor Day (November 2019)
127 slides from Agenus's investor day presentation, Nov 15, 2019
Slide 1: Agenus NASDAQ:AGEN
agenus ASDAQ:AGEN (in) (vy)
Slide 2: Forward-Looking Statements
Forward-Looking Statements This presentation contains forward-looking statements. These forward-looking statements are subject to risks and uncertainties, including the factors described under the Risk Factors section of our most recent Annual Report on Form 10-K or Quarterly Report on Form 10-Q fil
Slide 3: Agenus
Agenus Garo Armen, PhD, Chairman and CEO
Slide 4: Agenda
11:00 - 11:10am Agenus Vision Garo Armen, PhD 11:10 - 11:20am Agenus: Who We Are And Where We are Going Jennifer Buell, PhD Oncology: What Is Working and How Can We Improve? 11:20 - 11:50am Dr. Manuel Hidalgo A Cervical Cancer Overview 11:50 - 12:05pm Agenus Zalifrelimab and Bastilimab in Cervical C
Slide 5: Cancer and the Immune System - A Tug of War
Cancer and the Immune System - A Tug of War
Slide 6: Agenus Is Set Up for Proprietary and Optimal Combinations
Agenus Is Set Up for Proprietary and Optimal Combinations Checkpoint Antibodies Neoantigen Cancer Vaccines Cell Therapy Immune Adjuvants 6
Slide 7: Agenus Has Several Notable Strategic Partners
Agenus Has Several Notable Strategic Partners $2.4+ billion in potential milestones & royalties; $500M+ already received $172.5M $145M $10M $9M $190M received1 received2 received received received3 Eligible Eligible Eligible Eligible Eligible • $1.7Bn milestones • $450M milestones • $200M milestones
Slide 8: Imperative To Deliver Accessible Curative Combinations, Fast
Imperative To Deliver Accessible Curative Combinations, Fast Transformation 1994-2014 2014 2015 Antigen vaccines Antibodies Proprietary QS-21 (SHINGRIX) antigens 2015 2016 2019 GMP Fc engineering >14 proprietary programs manufacturing Cell line 13 INDs & 12 Clinical development combos 4 notable part
Slide 9: DRG Index
uity DRG Index - Last Prio
Slide 10: Agenus: Who We Are And Where We are Going
Agenus: Who We Are And Where We are Going Jennifer Buell, PhD, Chief Operating Officer
Slide 11: Agenus Leadership Team
Agenus Leadership Team Garo Armen, PhD Jennifer Buell, PhD Julie DeSander Chief Executive Officer Chief Operating Officer VP Business Development & Alliances • Founder of Agenus and pioneer in • Led research and clinical efforts to • Led $1.7B transaction with Gilead and multiple immuno-oncology adv
Slide 12: Agenus Drives Innovation with Record Speed
Agenus Drives Innovation with Record Speed • Pivotal trials - 200+ patients treated with AGEN2034 (PD-1) & AGEN1884 (First-Gen CTLA-4) Operational Execution • 13 INDs filed in 3.5 years; novel discoveries advance • Advanced proprietary combinations Strategic Partnerships • Balstilimab and zalfrelima
Slide 13: Agenus Neoantigen Vaccines Expose Tumors for Immune Killing
Agenus Neoantigen Vaccines Expose Tumors for Immune Killing Remarkable activity in some patients with metastatic melanoma disease free 10+ yrs Before 16 Months 32 Months Prophage Post-Treatment Post-Treatment Belli F et al., Clin Oncol 2002;20:4169-4180
Slide 14: Combinations are Critical for Robust & Durable Responses
Combinations are Critical for Robust & Durable Responses Launched Ph 2: KEYTRUDA plus Agenus vaccine with SOC (GBM) Funded by NIH BTTC; ongoing Ph2: Prophage combined with SOC XRT + Chemo Bloch et al. Clin Cancer Res. 2017: 14
Slide 15: Zalifrelimab is a Novel, Clinically Active, Anti-CTLA-4
Zalifrelimab is a Novel, Clinically Active, Anti-CTLA-4 zalifrelimab is advancing in a pivotal trial in combination with balstilimab in cervical cancer • Phase 1 Clinical Trial with Zalifrelimab • 62 y/o female with angiosarcoma of nose and cheeks had a complete and durable response (CR >2.8yrs) Fai
Slide 16: Agenus is Fully Integrated From Concept to Clinic
Agenus is Fully Integrated From Concept to Clinic 16
Slide 17: Agenus Outpaces Big Pharma in Advancing I-O Discoveries
Agenus Outpaces Big Pharma in Advancing I-O Discoveries Number of INDs (2016 - Present) 14 13 INDs# 12 10 1 Agenus program 8 4 Agenus programs 6 4 2 0 Astrazeneca Regeneron Pfizer Abbvie Incyte Amgen Novartis Roche BMS Merck Agenus Analysis as of August 2019 # INDs include programs partnered with In
Slide 18: Agenus 2015
Agenus 2015 Checkpoint Antibodies Program type CTLA-4 AGEN1884 Fully-owned PD-1 AGEN2034 Partnered GITR INCAGN1876 Option to Gilead OX40 INCAGN1949 TIM-3 INCAGN2390 LAG-3 INCAGN2385 Vaccines Glioblastoma (newly diagnosed) ProphageTM Adjuvants Shingles QS-21 Stimulon® Malaria 18 Notes: AGEN1884 and A
Slide 19: Agenus 2019
Mechanism/Target Product Partner Preclinical Phase 1 Phase 2 Phase 3 Filed Approved Checkpoint Antibodies CTLA-4 AGEN1884 Program type PD-1 AGEN2034 Fully-owned Next-generation CTLA-4 AGEN1181 Partnered TIGIT Option to Cytokine (bispecific) Gilead NK cell (bispecific) Stromal conditioning (bispecifi
Slide 20: Agenus First to Market Opportunity With CTLA-4 and PD-1
Agenus First to Market Opportunity With CTLA-4 and PD-1 • PD-1s represent the largest oncology product category, with multiple blockbuster products • Agenus’ PD-1 antibody (balstilimab) is on track for a BLA filing in 2020 • Recent clinical data has solidified the opportunity for PD-1/CTLA-4 combos
Slide 21: Balstilimab is Core to Agenus' & Partners' Combinations
Balstilimab is Core to Agenus’ & Partners’ Combinations Annual US Sales Potential Near-term Opportunity in 165M Cervical Cancer Time Label Expansion in Other Solid Tumors 2B Combinations with Third Party Assets 3B Combinations with AGENUS Pipeline 8B+ 21
Slide 22: 2019 Progress
2019 Progress
Slide 23: 2019 Progress in Proprietary Programs
2019 Progress in Proprietary Programs Agenus Fully Owned Programs ü Pivotal combination zalifrelimab and balstilimab – accrual & planned interim analysis complete ü Pivotal trial with balstilimab – accrual and planned interim analysis near complete ü AGEN1181 in-clinic; PD-1 combos planned 4Q2019 ü
Slide 24: 2019 Progress in Partnered Programs
2019 Progress in Partnered Programs Milestones exceed $22.5M in receivables Partnerships ü FDA acceptance of GS-1423 (first-in-class bifunctional molecule) $7.5M ü FDA acceptance of AGEN1223 (first-in-class bispecific molecule) $7.5M ü FDA acceptance of AGEN2373 (potentially best in class anti-CD137
Slide 25: What to Expect In The Next Months
What to Expect In The Next 12 Months 2019 and 2020 File (2) BLAs Clinical Data on 6 programs Pipeline • Balstilimab, zalifrelimab, AGEN1181, AGEN2373, AGEN1223, & allogeneic cell therapy File (2) INDs with First/Best in class Deliver milestones on current partnerships Partnerships • Expected ~$60M i
Slide 26: Agenus BOD Update – Nov 2019
26 Agenus BOD Update – Nov 2019
Slide 27: Dr. Manuel Hidalgo
Dr. Manuel Hidalgo Chief of the Division of Hematology and Medical Oncology at Weill Cornell Medicine and NewYork- Presbyterian/Weill Cornell Medical Center
Slide 28: Immunotherapy for Cancer Treatment: What is Working and What is Not
Immunotherapy for Cancer Treatment What is Working and What is Not Manuel Hidalgo, M.D., Ph.D. July 2019
Slide 29: Disclosure
Disclosure • Founder and stock holder: Champions Oncology, Inc. • Research support from: Celgene, Pfizer, Bioline, Asana, Erytech, Bicycle, Berg, Oncomatrix, BioExcell. • Honorarium from: Celgene, Bioline, Erytech, Agenus, SOBI, Pharmacyte, Bayer, Targovax, Oncomatrix, BioOncotech. • Royalties: Myri
Slide 30: Pillars of Cancer Treatment
Pillars of Cancer Treatment 30
Slide 31: Mechanism of Action of Check Point Inhibitors (Anti-PD-1)
Mechanism of Action of Check Point Inhibitors (Anti-PD-1) 31
Slide 32: Mechanism of Action of Check Point Inhibitors (Anti-CTLA-4)
Mechanism of Action of Check Point Inhibitors (Anti-CTLA-4) 32 32
Slide 33: Ipi + Nivo in Advanced Melanoma
Ipi + Nivo in Advanced Melanoma 33 Larkin at al, NEJM 2019
Slide 34: PDL1- Expression and Outcome
PDL1- Expression and Outcome 34 Hellman at al, NEJM 2019
Slide 35: PD1 Blockade in MSI Cancers
PD1 Blockade in MSI Cancers 35 Le et al., Science 2017
Slide 36: CPI in PDAC
CPI in PDAC 36 O’Reilly et at JAMA Onc 2019
Slide 37: Overview of IO Therapeutic Strategies
Overview of IO Therapeutic Strategies 37 Joyce at al, Science 2015
Slide 38: Effects on T cell Infiltrate in Tumor Tissues
Effects on T cell Infiltrate in Tumor Tissues 1600 D Cell Density (#Cells/mm2) Screening End of Cycle 2 1400 1200 1000 800 600 400 200 0 3 4 8 ce d SC C or R or D D D T te lls an m ) XC m ) C C C ic iva K+ 4+ D (P Tu C Tu -M ox ct G ot A K+ yt C an C (P 38 Hidalgo et al, ESMO 2018
Slide 39: Representative Case
Representative Case Figure 2 A B Baseline Week 8 39 Hidalgo et al, ESMO 2018
Slide 40: Individual Patient Outcome
Individual Patient Outcome Supplementary Figure 2 Sum of Longest Diameter Measured (mm) Days from Baseline (Monotherapy Day 5) Progression (N=19) Partial Response (N=1) Stable Disease (N=10) Non-Evaluable (N=7) 40 Hidalgo et al, ESMO 2018
Slide 41: Co-stimulatory Potential of CD137 Agonists: AGEN2373
Co-stimulatory Potential of CD137 Agonists: AGEN2373 Potent co-stimulator of the immune synapse ü Potent T cell activation and effector function ü Enhanced NK cell cytotoxicity ü IgG1 Fc backbone to realize full receptor agonism Improved Safety (expected) ü Conditionally active agonist avoid off-sit
Slide 42: AGEN1223 - A First-in-Class Bi-specific Designed to Deplete Regulatory T cells in TME
AGEN1223 - A First-in-Class Bi-specific Designed to Deplete Regulatory T cells in TME • Boosts cancer-fighting T effector cells • Spares important peripheral T regs • Targets co-expression of antigens on tumor-infiltrating T regs These important mechanisms not addressed with current therapies 42
Slide 43: Cervical Cancer Burden
Cervical Cancer Burden ~12,500 new cases in US annually 43
Slide 44: Cervical Cancer Facts
Cervical Cancer Facts 44 GOG 240
Slide 45: CPI (Anti-PD-1) in Cervical Cancer: Keynote 158
CPI (Anti-PD-1) in Cervical Cancer: Keynote 158 based on 14% RR in PD-1+ tumors (CPS>1) 45 Cancer Center Town Hall June 2019
Slide 46: CPI in Cervical Cancer: Checkmate 358
CPI in Cervical Cancer: Checkmate 358 46 Oaknin et al, ESMO 2019
Slide 47: Conclusions
Conclusions • PD 1 and CTL4 inhibition results in clear OS improvement is some cancer types (malignant melanoma, RCC, NSCLC). ü Biomarkers ü Toxicity ü Sequence ü Cost • PD-1 and CTLA 4 resistant patients/tumors need: ü Better drugs ü Other targets ü Combination strategies ü New strategies: ACT and
Slide 48: Balstilimab & Zalifrelimab Are Clinically Active and Advancing in Pivotal Trials
Balstilimab (anti-PD-1) & Zalifrelimab (anti-CTLA-4) Are Clinically Active and Advancing in Pivotal Trials Anna Wijatyk, MD, Head of Clinical Development and Operations
Slide 49: Balstilimab (AGEN2034) is Comparable to Commercial PD-1
Balstilimab (AGEN2034) is Comparable to Commercial PD-1 49
Slide 50: Zalifrelimab is a Novel Anti-CTLA-4 Comparable to Commercial CTLA-4
Zalifrelimab is a Novel Anti-CTLA-4 Designed to be Comparable to Commercial CTLA-4 50
Slide 51: Balstilimab in Patients with Solid Tumors & Relapsed/Refractory Cervical Cancer
Balstilimab in Patients with Solid Tumors & Relapsed/Refractory Cervical Cancer Anna Wijatyk, MD, Head of Clinical Development and Operations
Slide 52: Balstilimab Demonstrates Benefit in >60% of Patients in Multiple Tumors
Balstilimab Demonstrates Benefit in >60% of Patients in Multiple Tumors Data reported at ESMO 2018 Partial Response Durable disease stabilization (>12 weeks) Ovarian Cancer Ovarian Cancer Ovarian Cancer Cervical Cancer Ovarian Cancer Ovarian Cancer Breast Cancer Cervical Cancer Ovarian Cancer Cervic
Slide 53: Balstilimab Shows Durable Responses & Disease Control in Ovarian
Balstilimab Shows Durable Responses & Disease Control in Ovarian Phase 2 dose of 3mg/kg Q2W or 300mg Q3W 53
Slide 54: Zalifrelimab Designed to Be Comparable to Commercial Agents
Zalifrelimab Designed to Be Comparable to Commercial Agents Zalifrelimab is advancing in a pivotal trial in combination with balstilimab in cervical cancer Phase I Overview Complete Response – Durable beyond 2.8yrs and ongoing • Tolerable to 6mg/kg Q3W • Monotherapy was clinically active across a ra
Slide 55: Where PD-1 is Active, CTLA-4 Expands Response & Durability
Where PD-1 is Active, CTLA-4 Expands Response & Durability CTLA-4 enhances the efficacy of anti PD-1s, CTLA-4 enhances durability of response doubling it in some cancers 1L melanoma data from Checkmate-067 (n=945) Anti PD-1 Anti CTLA-4 + Anti PD-1 I-O combination in patients previously on chemothera
Slide 56: Two Paths For Fast Approval with Potential Best In Class Efficacy
Two Paths For Fast Approval with Potential Best In Class Efficacy Rapid Path to BLA Additional studies 2L Cervical Cancer Multiple Cancers • Accelerated FDA approval validated by • Potential to substantially expand initial market by Merck/others with monotherapy and combination moving to 1L cervical
Slide 57: Pivotal Trial of Balstilimab Monotherapy in Advanced Tumors and Cervical Cancer
Pivotal Trial of Balstilimab Monotherapy in Advanced Tumors and Relapsed/Refractory Cervical Cancer Key Inclusion Criteria Dose Escalation (phase 1)* Dose Expansion (phase2) Phase 2 • Histologically or cytologically Part I: AGEN2034 1,3,10 mg/kg q2w Primary endpoints: confirmed locally advanced or r
Slide 58: C-700-001 Study Responders
C-700-001 Study Responders Patient #1 – Continuing on treatment since May 2018 Central review % size #1 120 100 80 60 40 20 0 weeks Screening Cycle 36 – CR 0 10 20 30 40 50 60 70 80 Demographics 64 y.o.; White Baseline On-treatment Primary tumor FIGO-IIIa; SCC, Target lesions mediastinal l.ns. 36 mm
Slide 59: C-700-001 Study Responders
C-700-001 Study Responders Patient #2 – Treated for 52 weeks (until development of breast ca) Central review #2 Baseline On-treatment Screening 120 Target lesions Supraclavicular and hilar l.ns PR confirmed 36 mm CR – unconfirmed 100 Non-target lesions Paratracheal, paraaortic and absent peritoneal
Slide 60: Zalifrelimab and Balstilimab in Patients with Solid Tumors & Cervical Cancer
Zalifrelimab and Balstilimab in Patients with Solid Tumors & Relapsed/Refractory Cervical Cancer Anna Wijatyk, MD, Head of Clinical Development and Operations
Slide 61: Pivotal Trial of Balstilimab & Zalifrelimab Combination Therapy
Pivotal Trial of Balstilimab & Zalifrelimab Combination Therapy in Advanced Tumors and Relapsed/Refractory Cervical Cancer Phase 2 Key Inclusion Criteria Dose Escalation Dose Expansion Primary endpoints: Objective Response Rate (ORR) per AGEN1884 1mg/kg q6w • Histologically or cytologically RECIST 1
Slide 62: C-550-001 Study Responders
C-550-001 Study Responders Patient #3 – Continuing on treatment since Jan 2019 central review Baseline On-treatment % size #3 120 Target lesions Liver 83 mm PR: 28 mm on wk. 36 Screening 100 Non-target lesions Pelvic l.n. Absent on wk 36 80 60 40 20 0 0 5 10 15 20 25 30 weeks 35 40 Demographics 38 y
Slide 63: C-550-001 Study Responders
C-550-001 Study Responders Patient #4 – Continuing on treatment since Mar 2019 Site review % size #4 120 100 Screening 80 60 40 20 Week 27 – CR weeks from week 6-on 0 0 5 10 15 20 25 30 35 40 Baseline On-treatment Demographics 57 y.o.; white Target lesions Vaginal stump 47 mm; CR on wk 6 inguinal l.
Slide 64: Upcoming Catalysts for Balstilimab and Zalifrelimab
Upcoming Catalysts for Balstilimab and Zalifrelimab 2019* 2020 Complete Accrual for BLA trials File (2) BLAs Accelerate combination of balstilimab & Complete planned interim analysis AGEN1181 (NexGen CTLA-4) Commercial supply ready Additional strategy clinical collaborations 64
Slide 65: Dr. Steven J. O'Day
Dr. Steven J. O’Day Executive Director of the John Wayne Cancer Institute and Cancer Clinic Director of Providence Los Angeles Regional Research Professor of Medical Oncology and Director of Immuno- Oncology Co-Director of Melanoma and Cutaneous Oncology Research Program
Slide 66: The Revolution of Immuno-Oncology: Past, Present and Future
The Revolution of Immuno-Oncology Past, Present and Future Steven O’Day MD Professor of Medical Oncology Executive Director Director Clinical Research The John Wayne Cancer Institute Providence Saint John’s Health Center Santa Monica, CA 66
Slide 67: Outline
Outline lRevolution Immune Oncology lResurgence of CTLA-4 Blockade lComplex Tumor and Immune Dance lForward Progress 67
Slide 68: Immune System
Immune System lPower lAdaptability lMemory 68
Slide 69: Tumor Immunology: Overview
Tumor Immunology: Overview 69 Courtesy of Scott Gettinger, MD – Yale
Slide 70: Presented By Jedd D. Wolchok, MD, PhD at 2013 ASCO Annual Meeting
[TITLE] 70 Presented By Jedd D. Wolchok, MD, PhD at 2013 ASCO Annual Meeting
Slide 71: Targeting the Exhausted T-cell Phenotype
Targeting the Exhausted T-cell Phenotype • T cell exhaustion characterized by up-regulation of inhibitor checkpoint markers (CTLA-4, PD-1, LAG3..) • Exhaustion is proportional to # inhibitory markers • Blockade of these inhibitory receptors may restore functionality to T 71 cells Adapted from Wherry
Slide 72: Phase III Study of Ipilimumab, gp100, or Both in Advanced Melanoma
Phase III Study of Ipilimumab, gp100, or Both in Advanced Melanoma: Survival 1.0 Ipilimumab + gp100 (A) Ipilimumab alone (B) 0.9 gp100 alone (C) 0.8 0.7 Proportion Alive 0.6 Comparison HR P Value 0.5 Arms A vs C 0.68 .0004 Arms B vs C 0.66 .0026 0.4 0.3 0.2 0.1 0 1 2 3 4 72 Yrs Hodi FS, O’Day S et a
Slide 73: Overall survival
New combinations and better patient selection 100% New combos & better patient selection Overall survival PD-1 + CTLA-4 blockade PD-1 blockade CTLA-4 blockade No treatment Time 9th European Post-Chicago Melanoma/Skin Cancer Meeting Adapted from A. Ribas, Munich | Germany | June 20th, 2019 WCM 2013 7
Slide 74: Five-Year Survival with Combined Nivolumab and Ipilimumab
74 6 te NEW ENGLAND eS) JOURNAL of MEDICINE | ORIGINAL ARTICLE Five-Year Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma J. Larkin, V. Chiarion-Sileni, R. Gonzalez, J.-J. Grob, P. Rutkowski, C.D. Lao, C.L. Cowey, D. Schadendorf, J. Wagstaff, R. Dummer, P.F. Ferrucci, M. Smylie,
Slide 75: Overall Survival
• CheckMate 067 Overall Survival NIVO+IPI NIVO IPI 100 • Improved OS with NIVO+IPI (n = 314) (n = 316) (n = 315) 90 and NIVO vs IPI over 5 years Median OS, mo (95% CI) NR (38.2‒NR) 36.9 (28.2‒58.7) 19.9 (16.8‒24.6) 80 HR (95% CI) vs IPI 0.52 (0.42‒0.64) 0.63 (0.52‒0.76) – 70 64% HR (95% CI) vs NIVOa
Slide 76: Higher Proportion of Patients Alive and Treatment-Free at 5 Years
CheckMate 067 Higher Proportion of Patients Alive and Treatment-Free at 5 Years With NIVO+IPIa Population analyzed: patients who were alive and followed on study On study therapy Received subsequent systemic therapy Treatment-free (off study treatment and never received subsequent systemic therapy)
Slide 77: Cohort A: Nivolumab + Ipilimumab Intracranial Response
Cohort A: Nivolumab + Ipilimumab Intracranial Response All patients (n=35) No previous BRAFi+MEKi (n=27) IC RR = 51% IC RR = 59% Previous BRAFi+MEKi ORR = 25% (2/8) Presented by Georgina V Long @ProfGLongMIA 77
Slide 78: Overall Survival
Overall Survival A: Nivo+Ipi B: Nivo C: Nivo N=35 N=25 N=16 Total No Events, n (%) 16 (46%) 15 (60%) 13 (81%) Med. OS, mo (95% CI) 32.8 (11.9 - NR) 26.1 (6.93 - NR) 5.1 (1.8 - NR) 3-yr OS rate, % (95% CI) 49% (32-75) 42% (26-68) 19% (7-52) Overall Survival 63% 63% 60% 51% 49% 31% 42% 19% 19% Present
Slide 79: Returning to CTLA-4
Returning to CTLA-4 lImproving Efficacy lReduced Toxicity 79
Slide 80: PD1/CTLA-4 Platform
PD1/CTLA-4 Platform lFull dose PD1 lLow Dose CTLA-4 –1 mg/kg Q 3-12 weeks lPreserved Efficacy, Reduced Toxicity lMelanoma, RCC, NSCLC 80
Slide 81: Going Forward: Optimal IO Development
Going Forward Optimal IO Development – First Line Combination • PD1/CTLA-4/New Drug • PD1/New Drug – Second Line Combination • PD1/CTLA-4/New Drug • PD1/New Drug • CTLA4/New Drug 81
Slide 82: Going Forward: Optimal IO Clinical Trial Design
Going Forward Optimal IO Clinical Trial Design l Metastatic Disease – 12-18 month Landmark PFS plateau l Neoadjuvant – pCR, RFS l High Risk Adjuvant – RFS 82
Slide 83: Future Clinical Trials
Future Clinical Trials l Biology Driven and Translational l Adaptive and Smart l Clinically Meaningful Endpoints 83
Slide 84: Moving Forward: IO Platform Combinations
Moving Forward: IO Platform Combinations: l T Cell Optimization l Priming Response l TME 84
Slide 85: T-Cell Immune Checkpoints
T-Cell Immune Checkpoints 85 Presented By Scott Gettinger at 2014 ASCO Annual Meeting
Slide 86: Immune phenotypes and immunotherapy
Immune phenotypes and Trafficking immunotherapy 4 Immune excluded Priming & 3 activation Tumor cells Tumor 5 infiltration Immune desert / Antigen Tumor No T cells 2 6 presentation recognition Inflamed 1 7 Adapted from • Chen & Mellman, Immunity, 2013 Antigen Tumor • Kim & al. Ann Oncol, 2016 release
Slide 87: Potential combination strategies for the treatment of cancer
Potential combination strategies for the treatment of cancer Immunotherapy plus Immunotherapy plus radiotherapy immunotherapy Potential combinations Immunotherapy plus Immunotherapy plus targeted therapy chemotherapy 87
Slide 88: Final Thoughts
Final Thoughts l The Immune Cascade is Complex and Beautiful in its Memory, Adaptability and Durable Power l Cancer Cell Directed Therapies Can Be Effective But Fraught with Peril Due To Genetic Heterogeneity and Resistance l Going Forward, Short Bursts of Cancer Cell Directed Therapy in Combination
Slide 89: Agenus
agenus (in) (¥)
Slide 90: AGEN1181 - Next Generation Anti-CTLA-4
AGEN1181- Next Generation Anti-CTLA-4: Translating new insights into high-impact drug discovery Dhan Chand, PhD, Head of Drug Discovery
Slide 91: AGEN1181 Competitive Advantage - Monospecific Approaches
AGEN1181 Competitive Advantage - Monospecific Approaches AGEN1181 YERVOY® T cell activation ++ + Treg Depletion + ? Enhanced T cell priming and Memory + - Safety + - 91
Slide 92: AGEN1181 Competitive Advantages vs. CTLA-4 Bispecific Approaches
AGEN1181 Competitive Advantages vs. CTLA-4 Bispecific Approaches AGEN1181 CTLA-4 BISPECIFICS Target Cells + Limited Dosing Flexible Limited Optimal priming and Treg depletion via novel Fc mechanism + - Therapeutic Reach ++ Limited 92
Slide 93: 2nd Generation I-O: Optimizing CTLA-4 Therapeutic Benefit
2nd Generation I-O: Optimizing CTLA-4 Therapeutic Benefit (AGEN1181) AGEN1181 Enhanced Potency Next-Generation CTLA-4 ü Enhanced T cell priming/activation ü Increased intratumoral Treg depletion ü Improved combination efficacy anticipated (PD-1 and others) Improved Safety (expected) ü Reduced risk o
Slide 94: AGEN1181 Promotes Superior T cell Priming and Activation
AGEN1181 Promotes Superior T cell Priming and Activation Increased binding to FcγRIIIA enhances T cell responsiveness 12 A n ti- C T L A - 4 IL - 2 ( fo ld - c h a n g e ) 10 AG EN 1181 AGEN1181 B M S -lik e N G a n ti-C T L A -4 Afucosylated 8 IgG1 Y e rv o y -lik e 6 4 Is o ty p e c o n tr o l 2 h
Slide 95: AGEN1181 is Optimally Designed to Enhance Treg Depletion
AGEN1181 is Optimally Designed to Enhance Treg Depletion AGEN1181 Parental IgG1 Isotype Control 95 Source: Agenus Data
Slide 96: Superior Combination Activity with PD-1 Blockade
Superior Combination Activity with PD-1 Blockade A comparison to first-generation anti-CTLA-4 1. Enhances antibody function 2. Increases combination potential 3. Harnesses a novel MoA 96 Source: Agenus data Waight et al., Cancer Cell 2018
Slide 97: 2nd Generation I-O: Optimizing CTLA-4 Therapeutic Benefit
2nd Generation I-O: Optimizing CTLA-4 Therapeutic Benefit (AGEN1181) AGEN1181 Enhanced Potency Next-Generation CTLA-4 ü Enhanced T cell priming/activation ü Increased intratumoral Treg depletion ü Improved combination efficacy anticipated (PD-1 and others) Improved Safety (expected) ü Reduced risk o
Slide 98: AGEN1181 is Designed to Avoid the Risk of CDC-mediated AEs
AGEN1181 is Designed to Avoid the Risk of CDC-mediated AEs Advantage relative to IgG1 and afucosylated next-gen (BMS) approaches 2.5 2.0 Ig G 1 (Ip ilim u m a b -lik e ) O D 450 1.5 A fu c o s y la te d (B M S N e x tG e n -lik e ) 1.0 0.5 AG EN1181 0.0 0.1 1 10 100 A n t ib o d y ( µ g /m L ) • Ant
Slide 99: 2nd Generation I-O: Optimizing CTLA-4 Therapeutic Benefit
2nd Generation I-O: Optimizing CTLA-4 Therapeutic Benefit (AGEN1181) AGEN1181 Enhanced Potency Next-Generation CTLA-4 ü Enhanced T cell priming/activation ü Increased intratumoral Treg depletion ü Improved combination efficacy anticipated (PD-1 and others) Improved Safety (expected) ü Reduced risk o
Slide 100: AGEN1181 is Designed to Expand Benefit of Anti-CTLA-4
AGEN1181 is Designed to Expand Benefit of Anti-CTLA-4 FcγRIIIA polymorphism and neoantigen burden contributes to the activity of anti-CTLA-4 AGEN1181 is designed to benefit ~60% of patients (with & without the genetic polymorphism) • ~20% of patients have curative benefit with anti-CTLA-4 alone • ~4
Slide 101: AGEN1181 is Designed to Expand Benefit of Anti-CTLA-4
AGEN1181 is Designed to Expand Benefit of Anti-CTLA-4 FcgRIIIA polymorphism and neoantigen burden AGEN1181 demonstrates enhanced binding to contributes to the activity of anti-CTLA-4 both the low and high-affinity FcγRIIIA F/F 158 V/F or V/V 158 F/F 158 hIgG1 V/F or V/V158 hIgG1.N297A (Fc silent) AG
Slide 102: AGEN1181 Outperforms an IgG1 Analog in Low Affinity FcγRIIIA Donors
AGEN1181 Outperforms an IgG1 Analog in Donors That Express the Low Affinity FcγRIIIA 158F Allele FcγRIIIA 158 F/F donor FcγRIIIA 158 V/F donor AGEN1181 AGEN1181 IgG1 IgG1 Control Control F - low affinity allele V - high affinity allele 102 Source: Agenus Data
Slide 103: Rational Combinations Can Expand Therapeutic Benefit
Rational Combinations Can Expand Therapeutic Benefit Focal Radiation combines with NexGen CTLA-4 and PD-1 blockade to enhance tumor control (B16F10 tumor model) Focal Radiation (10Gy) Anti-PD-1 Anti-PD-1 Isotype Control Isotype Control + NG anti-CTLA-4 + NG anti-CTLA-4 4000 4000 4000 4000 T u m o r
Slide 104: AGEN1181 is Optimally Designed for Monotherapy and Combination Superiority
AGEN1181 is Optimally Designed for Monotherapy and Combination Superiority Two distinct and rapid paths to BLA approval 1. Monotherapy with deeper responses compared to first-generation CTLA-4 with expanded benefit in patients that are unresponsive due to a FcγR genetic polymorphism 2. Superior comb
Slide 105: VISION I-O Discovery Platform
VISION I-O Discovery Platform Cailin Joyce, PhD, Business Development & Alliance Management
Slide 106: Rate of approvals from oncology clinical trials
3.4% Rate of approvals from oncology clinical trials 106 Source: Wong, et al. Biostatistics 2019
Slide 107: VISION Capabilities and Applications
VISION Capabilities and Applications In vitro ecosystems Target discovery Systematic perturbations VISION Therapeutic optimization Computational framework Smart trials 107
Slide 108: Deep, Integrative Profiling of the Tumor-immune Interface In Vitro
Deep, Integrative Profiling of the Tumor-immune Interface In Vitro 108
Slide 109: Discovery: Combinations for Durable Anti-PD1 Response
Discovery: Combinations for Durable Anti-PD1 Response VISION T cell dysfunction VISION SEA assay Public scRNA-seq data Target expression on an activated, PD-1 Upregulated on activated T cells Enriched in intratumoral CD8+ T cells responsive T cell subset in presence of AGEN1181 Isotype Isotype Perip
Slide 110: Smart Trials: Predictive Signature for PD-1 Response
Smart Trials: Predictive Signature for PD-1 Response Agenus In vitro dysfunction signature 231 genes ** p=0.07 (Agenus) Bulk RNA-sequencing data from melanoma tumors Feldman et al., 2016 Melanoma TIL dysfunction signature • 14 PD-1 responders n.s. p=0.63 1088 genes (Feldman et al., 2016) • 13 PD-1 n
Slide 111: VISION Helps Develop a Broad Clinical Pipeline
VISION Helps Develop a Broad Clinical Pipeline C C 111
Slide 112: VISION Helps Develop a Broad Clinical Pipeline
VISION Helps Develop a Broad Clinical Pipeline 112
Slide 113: VISION Catalyzes Development and Discovery
VISION Catalyzes Development and Discovery ü Improve durability of PD-1 responses ü Deep read on AGEN1181 mechanisms of action ü Maximize potential of iNKT cells & other next-generation agents 113
Slide 114: AgenTus Therapeutics: New Generation of Cell Therapies
AgenTus Therapeutics New Generation of Cell Therapies November 2019 114
Slide 115: Leadership team
Leadership team Walter Flamenbaum M.D. Peter Suenaert, M.D., PHD Andy Hurwitz, PhD Marc van Dijk, PhD Chief Executive Officer Head of Global Clinical Head of Preclinical Research Head of Platform Development Development Mark Exley, PHD Michael Plater, PhD Alain Pralong, PHD Head of Cellular Immunolo
Slide 116: Leading with New Generation Cell Therapies
Leading with New Generation Cell Therapies Our cell therapies are designed to: • Be safer and more effective • Be more affordable • Target solid tumor cancers – not treated with currently approved cell therapies • Achieve durable responses when used with Agenus checkpoint antibodies AgenTus advantag
Slide 117: First Generation Cell Therapies Have significant limitations and challenges
First Generation Cell Therapies Have significant limitations and challenges Current cell therapies Product Cost (US) Production Time • Only two approved therapies $475,000 22 days • Both are autologous CAR-T cell based $373,000 26 - 29 days • Both address only B-cell leukemias and lymphomas Total tr
Slide 118: First Generation Cell Therapies: Great when they work but...
First Generation Cell Therapies Great when they work but….. Positives • Unprecedented efficacy and durability in “liquid” cancers Hurdles • Must be individually made - for each patient • Take a month to manufacture • Costly - up to $1M total treatment cost per patient • Failure to manufacture - one
Slide 119: Making Cell Therapies More Effective, Safer, Cheaper and Broadly Applicable
Making Cell Therapies More Effective, Safer, Cheaper and Broadly Applicable requires… NEED TO HAVE A Superior Optimal New Low 1 Cell Format 2 Receptors 3 Targets 4 Manufacturing Cost Current efforts generally aim to improve on just one aspect of these which is not sufficient to achieve the desired o
Slide 120: Advantage: a New Generation Adoptive Cell Therapy
Advantage: a NEW GENERATION Adoptive Cell Therapy (“ACT”) OUR CAPABILITIES (3) Our proprietary Potent cancer-killing Our precision 1 with our flexible 2 engineered 3 novel Our TARGETS proprietary 4 Rapid, lower cost novel TARGETS PRODUCTION PROCESS CELL FORMAT RECEPTORS T-Rx™, Intrepid ™, Phosphopep
Slide 121: Natural Killer T Cells (iNKTs): Powerful Multipurpose Cancer Killers
Natural Killer T Cells (“iNKTs”): Powerful Multipurpose Cancer Killers spearheading iNKTs for 3rd generation ACT Invariant Lipid • Have two natural mechanisms for killing TCR antigen CD1d cancer cells – Invariant T Cell Receptor (“iTCR”) detects iNKT Tumor tumor target CD1d & kills cell cell – NKG2D
Slide 122: iNKT Cells Also Significantly Boost Immune Response Naturally
iNKT Cells Also Significantly Boost Immune Response Naturally IL-12 • Recondition Tumor Micro-Environment (“TME”) – Strong interferon gamma secretion TAM boosts effector T cell recruitment iNKT or cell APC • Activate antigen presenting cells for better GzmB/FasL recognition of tumors by targeting mu
Slide 123: iNKT Cells are Ideally Suited to Treat All Types of Late Stage Cancers
iNKT Cells are Ideally Suited to Treat All Types of Late Stage Cancers Allogeneic iNKTs IND 4Q 2019, with clinical trials for mono and combinations in 2020 • Optimal Treatment : Allogeneic iNKT + Agenus checkpoint antibodies • Designed to treat most late-stage cancer patients - 1st and 2nd gen cell
Slide 124: Allogeneic iNKT Cells
Agenlus Allogeneic iNKT Cells THERAPEUTICS : Updo) gz >. 2 ( Es SZ (0) si ~o& 2 2 Leukapheresis a. ; . a " ; Zz Healthy donors from 1 healthy donor Purification Expansion Freezing & consolidation Infusion for ~1000 patients to many patients ‘of stock AVAILABLE AS NEEDED 4+ weeks manufacturing SS g G
Slide 125: Clinical Plans to Provide Optimal, Stepwise Validation of Cell Therapy
Clinical Plans to Provide Optimal, Stepwise Validation of Cell Therapy Potent cancer-killing, Precision engineered New Fast, cost-effective Optimal 1 Flexible CELL FORMAT 2 receptors 3 targets 4 production process 5 combinations Clinical Trial Plan • Efficacy against solid and liquid tumors Allogene
Slide 126: AgenTus Therapeutics
AgenTus Therapeutics Third Generation Cell Therapies R&D Day Presentation For additional information please contact: Walter Flamenbaum, M.D. CEO AgenTus Therapeutics, Inc. walter.flamenbaum@agentustherapeutics.com 1 (917) 754 0229 V 5.1 11 07 2019 126
Slide 127: agenus
agenus (in) (¥)