Agenus Inc. · NASDAQ:AGEN
Agenus — Investor Day (February 2020)
87 slides from Agenus's investor day presentation, Feb 20, 2020
Slide 1: Corrections note to presentation
This version of the presentation includes corrections to errors in the original presentation contained on slide 22, clarifying footnotes on slides 20 & 21, and a post-meeting addition (slide 23).
Slide 2: Forward-Looking Statements
Forward-Looking Statements This presentation contains forward-looking statements that are made pursuant to the safe harbor provisions of the federal securities laws, including statements regarding Agenus and AgenTus' clinical development and regulatory plans and timelines, expected timing for clinic
Slide 3: We aim to have cancer patients living longer and better
WE AIM TO HAVE CANCER PATIENTS LIVING LONGER AND BETTER 3
Slide 4: Investor Day
Investor Day • Pivotal Trial Clinical Data on Balstilimab and Zalifrelimab • AGEN1181: Beyond a Next-Generation CTLA-4 • New Discoveries From the Experts From Agenus Garo Armen, PhD Dhan Chand, PhD Chairman and CEO Head of Drug Discovery Jennifer Buell, PhD Mark Exley, PhD President and COO Vice Pre
Slide 5: Delivering Some of Our 2020 Goals Today
Delivering Some of Our 2020 Goals Today • 6 Clinical Data Readouts • 2 INDs ! Zalifrelimab and Balstilimab • 2 BLA filings ! Balstilimab ! AGEN1181 AGEN1223 AGEN2373 GS-1423 5 *2020 Objectives Shared at Agenus’ November 2019 R&D Day
Slide 6: Dr. Bradley J. Monk
Dr. Bradley J. Monk MD, FACOG, FACS • Professor of Gynecologic Oncology • University of Arizona • Arizona Oncology (US Oncology Network) • Co-Director > GOG Partners • Chair Cervical Cancer Committee > Gynecologic Cancer Intergroup (GCIG) 6
Slide 7: The Enemy
The Enemy 7
Slide 8: Three Decades: Recurrent & Metastatic Cervical Cancer
Three Decades: Recurrent & Metastatic Cervical Cancer • Seven randomized phase 3 trials • Cisplatin (Cis) 50 mg/m2 plus paclitaxel (Pac) 135 mg/m2 IV over 24 hrs standard therapy • Median overall survival (OS) ≤12 months • Majority of patients with recurrent cervical cancer pre-treated with cisplati
Slide 9: New England Journal of Medicine and The Lancet
New England Journal of Medicine and THE LANCET Bevacizumab for advanced cervical cancer: final overall survival and adverse event analysis of a randomised, controlled, open-label, phase 3 trial (Gynecologic Oncology Group 240) Krishnansu S Tewari, Michael W Sill, Richard T Penson, Helen Huang, Lois
Slide 10: FDA Accelerated Approval of Pembrolizumab
FDA Accelerated Approval of Pembrolizumab (June 12, 2018) ORR 14.3% (95% CI; 7.4, 24.1) Companion Diagnostic PD-L1 IHC 22C3 CPS≥1 10 FDA Press Release. https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm610572.htm. Accessed October 31, 2019.
Slide 11: Nivolumab + Ipilimumab in Cervical Cancer: CheckMate 358
Efficacy and Safety of Nivolumab + Ipilimumab in Patients with Recurrent/Metastatic Cervical Cancer: Results From CheckMate 358 Proof of Concept for Combo PD-1 + CTLA-4 in Cervical R. Wendel Naumann1*, Ana Oaknin2*, Timothy Meyer3, Jose Maria Lopez-Picazo4, Christopher Lao5, Yung-Jue Bang6, Valentin
Slide 12: Study Design and Current Analysis
CheckMate 358 Study Design and Current Analysis Randomized cervical cancer cohorts of CheckMate 358 (NCT02488759) testing 2 combination regimens of nivolumab + ipilimumab for R/M disease Screening Treatment Follow-up Current Analysis (until toxicity or progression or a maximum of 24 mo) NIVO+IPI Reg
Slide 13: Patient Characteristics
CheckMate 358 Patient Characteristics NIVO3+IPI1 NIVO1+IPI3 NIVO3+IPI1 NIVO1+IPI3 Baseline characteristics (n = 45) (n = 46) Prior therapies (n = 45) (n = 46) Age, median (range), y 48.0 (32–76) 44.5 (26–74) Prior therapy, n (%) Platinum 39 (86.7) 42 (91.3) ECOG PS, n (%) Bevacizumab 24 (53.3) 25 (5
Slide 14: Change from Baseline in Target Lesion Size
CheckMate 358 Change from Baseline in Target Lesion Size NIVO3+IPI1 NIVO1+IPI3 No PST for R/M disease No PST for R/M disease baseline in target lesions (%) baseline in target lesions (%) 100 PST for R/M disease 100 PST for R/M disease Maximum change from Maximum change from 75 75 50 50 25 25 0 0 −25
Slide 15: Complete Response to Treatment with Nivolumab + Ipilimumab
CheckMate 358 Complete Response to Treatment with Nivolumab + Ipilimumab 42-year-old woman with recurrent stage IIA (with lung metastases) CD4 HPV positive SCC of the cervix; ECOG PS 1; tumor cell PD-L1 <1% Baseline Before CheckMate 358 • First diagnosed with localized disease January 2016 • Prior t
Slide 16: CheckMate 358 Safety Summary
CheckMate 358 CheckMate 358 Safety Summary NIVO3+IPI1 NIVO1+IPI3 (n = 45) (n = 46) Event, n (%) Any grade Grade 3–4 Any grade Grade 3–4 TRAEs 36 (80.0) 13 (28.9) 38 (82.6) 17 (37.0) Treatment-related SAEs 12 (26.7) 8 (17.8) 16 (34.8) 10 (21.7) TRAEs leading to treatment 6 (13.3) 2 (4.4) 9 (19.6) 6 (
Slide 17: CheckMate 358 TRAEs with Incidence ≥5%
CheckMate 358 CheckMate 358 TRAEs with Incidence ≥5%* NIVO3+IPI1 NIVO1+IPI3 (n = 45) (n = 46) TRAEs, by SOC, n (%) Any grade Grade 3–4 Any grade Grade 3–4 General/administration site 17 (37.8) 0 20 (43.5) 0 Gastrointestinal 16 (35.6) 4 (8.9) 26 (56.5) 6 (13.0) Skin 16 (35.6) 0 16 (34.8) 2 (4.3) Labo
Slide 18: Why CTLA-4 and PD-1 have Best-in-Class Potential
Why CTLA-4 and PD-1 have Best-in-Class Potential 18
Slide 19: CTLA-4 Improves PD-1 Responses & Durability in Multiple Tumors
CTLA-4 Improves PD-1 Responses & Durability in Multiple Tumors Previously treated MSI-H CRC 34% 58% PD1 ORR 1L Melanoma 45% 57% PD1/CTLA4 ORR 1L NSCLC (≥50% PD-L1) 37% 45% 1L RCC 36% 41% 2L+ Bladder cancer 21% 38% 1L NSCLC (≥1% PD-L1) 28% 36% Ovarian cancer 12% 31% 2L+ Hepatocellular cancer 20% 31%
Slide 20: Balstilimab Alone is Active and Durable in 2L Cervical Cancer
Balstilimab (anti-PD-1) Alone is Active and Durable in 2L Cervical Cancer (11.9% ORR;1 CR, 4 PRs)*, Independent Reads CRs & PRs show durability >70wks *Agenus data: C-700-01 interim analysis data cut off 16 Oct 2019. Estimates for efficacy set (n=42) – all patients with measurable disease at baselin
Slide 21: Balstilimab + Zalifrelimab in 2L Cervical Cancer
Balstilimab (anti-PD-1) + Zalifrelimab (anti-CTLA-4) may be a Best-in-Class Option in 2L Cervical Cancer (20.6% ORR, 3 CR, 4PR)*, Independent Reads Balstilimab 3mg/kg Q2W Zalifrelimab 1mg/kg Q6W CRs & PRs show durability >50wks *Agenus data: C-550-01 interim analysis data cut off 12 Jul 2019 with 1
Slide 22: Balstilimab plus zalifrelimab may be most promising off-the-shelf option
Balstilimab (anti-PD-1) plus zalifrelimab (anti-CTLA-4) may be the most promising & clinically advanced off-the-shelf treatment option with an acceptable safety profile Sponsor Agent # of ORR CR PR Related AEs Patients (Grade 3+) Agenus Balstilimab* 42 14.3% 2.4% 11.9% 9.1% Merck Pembrolizumab*** 98
Slide 23: Agenus CTLA-4 & PD-1 Potential Best-in-Class Option for 2L Cervical Cancer
Agenus CTLA-4 & PD-1 Potential Best-in-Class Option for 2L Cervical Cancer # of Complete Partial Overall Sponsor Treatment Patients Response Response Response Rate Combination of PD-1 and CTLA-4 Balstilimab + Agenus 34 8.8% 11.8% 20.6% Zalifrelimab* Ipilimumab + BMS 26 3.8% 19.2% 23.1% Nivolumab1 PD
Slide 24: Clinical Benefit with Tolerability in 2L Cervical Cancer Studies
Clinical Benefit with Tolerability in 2L Cervical Cancer Studies with Balstilimab (anti-PD-1) and Zalifrelimab (anti-CTLA-4) Balstilimab*+ Balstilimab** Zalifrelimab (N=44) (N=41) Serious on-treatment AEs, n (%) [#AEs] 15 (36.6%) [24] 22 (50.0%) [44] Grade 3+ on-treatment Adverse Events, n (%) [#AEs
Slide 25: Conclusions
Conclusions 1. Recurrent cervical cancer is an area of high unmet need 2. Accelerated approval from small single arm clinical trials is established as a pathway to the clinic 3. Anti PD-L1 has activity (ORR) between 10-15% a) Including Balstilimab 4. Adding anti CTLA-4 to anti PD-L1 increases clinic
Slide 26: Anna Wijatyk, MD, Head of Clinical Development
WE AIM TO HAVE CANCER PATIENTS LIVING LONGER AND BETTER Anna Wijatyk, MD Head of Clinical Development 26
Slide 27: On Track to Deliver BLAs: Balstilimab & Zalifrelimab
On Track to Deliver 2 BLAs: Balstilimab & Zalifrelimab 27
Slide 28: Balstilimab Monotherapy Complete Response Case
Balstilimab (PD-1) Monotherapy Complete Response Case Patient #1 – Continuing on treatment since May 2018 Independent review 120 100 % Tumor size 80 60 40 20 0 0 10 20 30 40 50 60 70 80 Screening Cycle 36 – CR Weeks Demographics 64 y.o.; White Baseline On-treatment Primary tumor FIGO-IIIa; SCC, Targ
Slide 29: Combination Balstilimab & Zalifrelimab Complete Response
Combination Balstilimab (PD-1) & Zalifrelimab (CTLA-4) Complete Response (Overall 3 CRs; 4 PRs) 120 100 Screening % Tumor size 80 60 40 20 Week 27 – CR 0 from week 6-on 0 5 10 15 20 25 30 35 40 Weeks Baseline On-treatment Demographics 57 y.o.; white Target lesions Vaginal stump 47 mm; CR on wk 6 ing
Slide 30: Clinical Development and Operations
Clinical Development and Operations 2 Interim Analyses 8 Studies Open Pivotal Trial Analysis Underway ~300 Patients Treated 25 Countries 54 Agenus Team 120 Sites Members 30
Slide 31: Deliver Clinical Data on Multiple Discoveries
Deliver Clinical Data on Multiple Discoveries Balstilimab Balstilimab + Zalifrelimab AGEN1181 AGEN1223 AGEN2373 31
Slide 32: New Discoveries to Patients with Path-breaking Speed
New Discoveries to Patients with Path-breaking Speed IND Cleared Sites Activated Patients Dosed Industry Standard: 168 days Agenus timelines - 65 Days Speed to clinic, speed to patients, speed to market 32
Slide 33: Agenus
Agenus Jennifer Buell, PhD President and COO 33
Slide 34: Agenus Discoveries In The Clinic
Agenus Discoveries In The Clinic Agenus Partners Commercial QS-21 (SHINGRIX)1 Balstilimab (PD-1) Pivotal Balstilimab + Zalifrelimab (Planned BLA 2020) (CTLA-4) GS-1423 MK-4830 AGEN1181 INCAGN1876 Phase 1/2 AGEN1223* INCAGN1949 AGEN2373* INCAGN2390 INCAGN2385 *Option programs w GILD 34 More detailed
Slide 35: Dr. Charles Drake
Dr. Charles Drake MD, PhD • Professor of Medicine • Co-Director, Cancer Immunotherapy Programs • Co-Leader, Tumor Biology and Microenvironment • Faculty Director – Human Immune Monitoring Core • Division Director – GU Oncology 35
Slide 36: Regulatory T Cells Are Prevalent in the Tumor Microenvironment
Regulatory T Cells (Treg) Are Prevalent in the Tumor Microenvironment Tumour antigen Regulatory CD4 T Cell TCR MHC (FoxP3+) +++ Tumour cell CD8 T cell PD-1 PD-L1 --- Suppressive Factors PD-1 PD-L2 --- -- - - - TCR MHC Tumour cell CD8 T cell +++ PD-L1 expression on tumor cells OR Myeloid cells SEND a
Slide 37: Targeted Treg Depletion Treats Cold Tumors
Targeted Treg Depletion Treats Cold Tumors (in mice) 37 Klages K., et al, Cancer Research 2010
Slide 38: Can a Cancer Vaccine Make A Cold Tumor Hot?
Can a Cancer Vaccine Make A Cold Tumor Hot? GVAX Vaccine in Prostate Cancer Endpoints High Risk PC Safety / Tolerability Randomize T Cell infiltration of prostate Arm A: Arm B: gland Androgen ADT Plus Vaccine Deprivation Therapy Profile the Tumor (ADT) Microenvironment Post- n=16 n=16 Treatment Surg
Slide 39: Increased CD8 Infiltration is Balanced by Treg Influx
In Human Prostate Cancer Increased CD8 Infiltration is Balanced by Treg Influx Adaptive Treg Resistance Untreated Androgen Androgen Control Deprivation Deprivation N = 13 Therapy PLUS Vaccine N=15 N=13 CD8+ T cell 96 (72–120) 205 (121–289) 263 (129–397) density (mean, 95%CI) Treg cell 29 (21–36) 59
Slide 40: In Murine Prostate Cancer Increased CD8 Infiltration is Balanced by Treg Influx
In Murine Prostate Cancer Increased CD8 Infiltration Ptprc Cd4 Cd8a is Balanced by Treg Influx (CD45) CD45 CD4 CD8a 102 102 102 Adaptive Treg Resistance relative to Pre-C * * Fold change *** 101 101 101 Pre-C Post-C D7 C-Resistant CD4+ T CD4+ T CD4+ T 100 100 100 C 7 nt C 7 nt C 7 nt D D D e- e- e-
Slide 41: CTLA-4 Is Highly Expressed on The Treg That Infiltrate Cancer
41 In Preparation Nirschl T and Drake C P B p m e F P K M C TL A 4 E xp res s io n P M B C M N C a 0 250 500 750 1000 1250 A iv c e ti v C a D te 4 P d B C That Infiltrate Cancer M D C 4 T re **** P T g B IL P T **** B P M B C re **** M M g C C N A a g A iv T . c e IL E ti v C x a D A p te 8 g e d .
Slide 42: Depleting Anti-CTLA-4 Cures a Fraction of Mice with Prostate Cancer
A Depleting Anti-CTLA-4 (IgG2a) Cures a Fraction of Mice with Prostate Cancer Degarelix Degarelix + αCTLA-4 (ND) 2000 Tumor volume (mm3) 2000 1500 1500 1000 1000 0% 0% 500 500 0 0 0 10 20 30 40 50 60 70 0 10 20 30 40 50 60 70 Days after degarelix Days after degarelix Degarelix + αPD-1 Degarelix + αC
Slide 43: Radiation Therapy Drives Adaptive Treg Resistance
B16/F10 RENCA MC38 105 105 105 10 4 15.6 10 4 22.7 10 4 23.0 Control 10 3 10 3 10 3 2 2 2 10 10 10 0 0 0 Foxp3 0 102 103 104 105 0 102 103 104 105 0 102 103 104 105 Radiation Therapy 105 105 105 10 4 31.7 10 4 41.8 10 4 50.0 RT Drives 103 103 103 2 2 2 10 10 10 0 0 0 Adaptive Treg 0 102 103 104 105
Slide 44: Depleting aCTLA-4 Plus Radiation Cures The Majority of Treated Animals
A Depleting aCTLA-4 Plus Radiation Cures The Majority Of Treated Animals 44 Marisciano, Drake et al Clinical Cancer Res 2018
Slide 45: RT + aCTLA-4 Cured Mice Show Long-Term Protection
100% of RT + aCTLA-4 Cured Mice Show Long-Term Protection Not the Case for RT + aPD-1 45
Slide 46: Selected aCTLA-4 Agents in the Clinic
Selected aCTLA-4 Agents in the Clinic Ipilimumab Tremilimumab BMS 928218 MK 1308 IgG Isotype IgG1 IgG2 Afucosylated Not Reported IgG1 Treg +/- No Not Reported Not Reported Depletion Grade III / IV ≈25% ≈15% Not Reported Not Reported IRAE 46 4
Slide 47: Optimized aCTLA-4 Product Profile
Optimized aCTLA-4 Product Profile • High Affinity for CTLA-4 • Fc Optimized to Enhance Depletion • Enhanced T Cell Activation • Promote T Cell Memory • Reasonable Tolerability 47
Slide 48: The Fc Engineered DLE Scaffold
The Fc Engineered “DLE” Scaffold 1. Enhances Binding to Human FcgRIIIa 2. Bind to both the f/f and v/v FcgRIIIa Variants IgG1 aCTLA-4 Fc Engineered aCTLA-4 48 Waight, JD et al, Cancer Cell 2018
Slide 49: Enhanced Treg Depletion with AGEN1181
Enhanced Treg Depletion with AGEN1181 AGEN1181 Parental IgG1 Isotype Control 49 Source: Agenus Data
Slide 50: Enhanced T Cell Activation with AGEN1181
Enhanced T Cell Activation with AGEN1181 Increased FcgRIIIa Binding (hIgG1-DLE) WT FcgRIIIa Binding (hIgG1) Absent FcgRIIIa Binding (hIgG1-N297A) Source: Agenus Data 50 Waight, JD et al, Cancer Cell 2018
Slide 51: Superior Combination Activity with PD-1 Blockade
Superior Combination Activity with PD-1 Blockade In comparison to first-generation anti-CTLA-4 Source: Agenus data 51 Waight et al., Cancer Cell 2018 5
Slide 52: Early Clinical Activity with AGEN1181
Early Clinical Activity with AGEN1181 • Ongoing Dose-Escalation Trial • Combination with Agenus’ aPD-1, balstilimab, initiated in Dec 2019 • 20 patients treated to date on monotherapy and in combination with balstilimab • 1 CR and disease stabilization in majority of response evaluable patients • Ba
Slide 53: Metastatic Endometrial Cancer: Confirmed Complete Response
Metastatic Endometrial Cancer: Confirmed Complete Response • 73 y/o Female with Endometrial Carcinoma (Uterine) – Initial Diagnosis 04-Nov-2015: Stage II – Prior treatment • TABHSO with Lymphadenectomy, • Carboplatin, Taxol, HDR Vaginal Cuff Radiation • Pembrolizumab • Incyte 107 (PI3K Inhibitor), •
Slide 54: A complete response to CTLA-4 monotherapy is noteworthy in solid tumors
A complete response to CTLA-4 monotherapy (AGEN1181) is noteworthy in solid tumors 1 CR (1mg/kg) & 2 SD durable (0.1 and 1mg/kg) seen with AGEN1181 Ipilimumab Monotherapy AGEN1181 Monotherapy • Most CRs in solid tumors are in melanoma • Stable disease in solid tumors outside of melanoma (endometrial
Slide 55: Summary / Forward Looking
Summary / Forward Looking • AGEN1181 is an Fc Enhanced Anti-CTLA-4 • Well-documented enhanced in vitro activity (Waight et al) • Potential for Enhanced Clinical Activity vs IgG1 (Ipilimumab) In combination with anti-PD-1 In combination with Radiation Therapy In combination with other Anti-Cancer The
Slide 56: Dr. Tyler Curiel
Dr. Tyler Curiel MD, MPH, FACP • Daisy M. Skinner President’s Chair in Cancer Immunology Research • Professor of Medicine and Microbiology, Immunology & Medical Genetics • University of Texas Health, San Antonio, TX 56
Slide 57: A Deeper Look
A Deeper Look ogenus
Slide 58: Endometrial Cancer Patient Complete Response
Endometrial Cancer Patient Complete Response • BRCA (-) • MSI stable • PD-L1 (-) • FcγRIIIA FF phenotype PATIENT UNLIKELY TO RESPOND TO IMMUNE THERAPY 58
Slide 59: AGEN1181 Selectively Expands an IFN-Responsive Memory CD8+ T Cell Population
AGEN1181 Selectively Expands an IFN-Responsive Memory CD8+ T Cell Population in vitro 3. Key insight: AGEN1181 selectively 1. K-means clustering & UMAP visualization expands an IFN type 1 responding 2. Conditional cell type differences Combined AGEN1181, AGEN1884 analog memory T cell isotype AGEN188
Slide 60: Response to ipilimumab + nivolumab correlates with expansion of γδ T cells
AGEN Discovery: Response to ipilimumab + nivolumab correlates with expansion of gamma delta (γδ) T cells in melanoma patients • Intratumoral CD45+ cells isolated from melanoma patients receiving ipilimumab + nivolumab • Single cells were sequenced using Smart-seq2 • AGEN analysis drives new mechanis
Slide 61: AGEN1181 enhances the γδ T cell response in vitro
Next-Generation Benefit: AGEN1181 enhances the γδ T cell response in vitro relative to 1st generation CTLA-4 Identify γδ T cell population Key insight: AGEN1181 (i) selectively expands and Comparable to intratumoral population (ii) may increase cytotoxic potential of γδ T cells in vitro γδ i. Freque
Slide 62: Conclusions
Conclusions • Uncovered potential cellular mechanisms underlying enhanced T cell responses to next generation CTLA-4 in pre-clinical studies • Next generation CTLA-4 benefit on memory-like T cell subset • Next generation CTLA-4 benefit on γδ T cell subset • Next experiments will expand observations
Slide 63: Next Steps
Next Steps 1. Make better killers • AGEN1181 (conventional T cells, gamma delta T cells) • CAR iNKT • Epitope prediction 2. Soften the battlefield • AGEN1181 (reduce regulatory T cells) • Bi-specific molecules (e.g., reduce myeloid cell effects, soluble factors or direct signals) 63
Slide 64: Our Next Wave of Innovation
OUR NEXT WAVE OF INNOVATION Dhan Chand, PhD Head of Drug Discovery 64
Slide 65: CD73-adenosine and TGFβ are Major Contributors to Therapeutic Resistance
CD73-adenosine and TGFβ are Major Contributors to Therapeutic Resistance 66
Slide 66: AGEN Solution: A Bi-functional Tumor Conditioning Agent
AGEN Solution: A Bi-functional Tumor Conditioning Agent CD73 binding region GS-1423* is potentially a first-in-class bi-functional antibody Phase I initiated Q2 2019 GS linker (*licensed to Gilead) TGFb-Trap 67
Slide 67: GS-1423 Enhances Tumor Cell Killing Alone and in Combination with anti-PD-1
GS-1423* Enhances Tumor Cell Killing Alone and in Combination with anti-PD-1 in a Suppressive Tumor Microenvironment 80 % Tumor Cell Killing GS-1423 + anti-PD-1 anti-PD-1 60 GS-1423 40 Isotype 20 0 0 20 40 60 80 Phase I initiated Time (hours) Q2 2019 68 *GS-1423 is licensed to Gilead by Agenus
Slide 68: Regulatory T Cells are a Potent Suppressive Barrier
Regulatory T Cells are a Potent Suppressive Barrier to Effective Anti- tumor Immune Responses 69
Slide 69: Bispecific Antibody for Selective Intratumoral Treg Depletion
AGEN Solution: Bispecific Antibody Designed for Selective Intratumoral Treg Depletion and T Cell Co-stimulation Target X Target Y AGEN1223 – first-in-class bispecific to: • Selectively deplete intratumoral Tregs • Enhance T cell effector function • Improve safety Phase I initiated December 2019 Fc-o
Slide 70: AGEN1223 Offers Dual Mechanism of TME Conditioning
AGEN1223 Offers Dual Mechanism of TME Conditioning and Effector T Cell Stimulation T re g Enhanced Treg depletion compared to mAbs or combination of mAbs AG EN 1223 5500 A n ti-G IT R (IN C A G N 0 1 8 7 6 ) a c tiv ity AGEN1223 4400 A n ti-O X 4 0 (A G E N 2 0 4 9 ) C C activity C o m b in a tio n
Slide 71: Tumor-associated Macrophages Adopt a Suppressive Phenotype
Tumor-associated Macrophages Adopt a Suppressive Phenotype and Attenuate Antitumor Immunity Tumor Macrophage Ligand expressed broadly across tumor types ITIMs SHP-1/2 Inhibitory receptor Phagocytosis M1 pro-inflammatory phenotype 72
Slide 72: Ligand-blocking Antagonist Antibody Designed to Repolarize Tams
AGEN Solution: Ligand-blocking Antagonist Antibody Designed to Repolarize and Enhance Function of Tams Tumor Ligand Macrophage AGEN1531 is a potential first-in-class antagonist antibody designed to: AGEN1531 • Repolarize tumor-associated macrophages ITIMs towards an M1 pro-inflammatory state Inhibit
Slide 73: AGEN1531 Antagonizes a Key Immunosuppressive Interface
AGEN1531 Antagonizes a Key Immunosuppressive Interface AGEN1531 converts macrophages from AGEN1531 relieves target-mediated immune suppressing to tumor fighting inhibition of FcγR signalling 80 600000 % M1 macrophages 60 400000 AGEN1531 RLU 40 200000 20 0 Isotype -3 -2 -1 0 1 2 0 Antibody (log µg/mL
Slide 74: Patient Progression on Anti-PD-1 Driven by Secondary Immune Checkpoints
Patient Progression on Anti-PD-1 Driven by Secondary Immune Checkpoints 75
Slide 75: Dual Functioning Bispecific AGEN1777
AGEN Solution: Dual Functioning Bispecific that Biases a Major T & NK Cell Immunoregulatory Interaction Towards Activation Tumor cell T / NK cell AGEN1777 is a potential first-in-class dual Ligand Co-stimulatory receptor antagonist bispecific AGEN1777 Inhibitory receptors APC FcγR Ligand Enhanced co
Slide 76: AGEN1777 Controls Tumors in a Mouse Colon Tumor Model
AGEN1777 Controls Tumors in a Mouse Colon Tumor Model Isotype Control anti-PD-1 AGEN1777 Bispecific (Bispecific) (mAb) (mouse surrogate) 2000 2000 2000 CR: 2/15 CR: 13/15 Tumor volume (mm3) Tumor volume (mm3) Tumor volume (mm3) 1500 1500 1500 1000 1000 1000 500 500 500 0 0 0 10 20 30 40 50 10 20 30
Slide 77: Novel Combinations Address Therapeutic Resistance
Novel Combinations Address Therapeutic Resistance Data Accepted for Presentation at AACR 2020 (Abstract #922) 78
Slide 78: Our next disruptors exemplify innovation and smart design
Our next disruptors exemplify innovation and smart design 79
Slide 79: Dr. Mark Exley
Dr. Mark Exley PhD • Affiliate, Harvard Medical School • Professorship, University of Manchester • Founder of NKT Therapeutics 80
Slide 80: Invariant NKT Cells Boost Immune Response Naturally
IL-12 INVARIANT NKT TAM or CELLS BOOST iNKT cell APC GzmB/FasL IMMUNE Cytotoxicity IFNɣ Activation IFNɣ RESPONSE IL-12 NATURALLY NK cell Tumor cell Cytotoxicity Mark Exley, PhD Principal 81
Slide 81: Invariant Natural Killer T (iNKT) Cells
Invariant Natural Killer T (iNKT) Cells Orchestrators of the immune system IL-12 iNKTs: • Suppress GvHD (no gene editing) Tumor • Home to tumor site iNKT cell associated Tumor • Massive expansion capacity >40,000 macrophages cell GzmB/FasL fold (1 healthy donor ~ 1000 doses) Cytotoxicity IFNɣ Activa
Slide 82: iNKTs May be Effective in Solid and Hematologic Tumors
iNKTs May be Effective in Solid and Hematologic Tumors Some cancers over-express CD1d Allogeneic iNKTs expected to enter clinic as mono and CPI combinations in 2020 • 1H2020: Safety with iNKT in Multiple Myeloma, CLL/SLL, iNHL (FL, MZL), and DLBCL • 2H2020: Safety and efficacy of iNKT and CPIs (i.e.
Slide 83: Smart Collaborations
SMART COLLABORATIONS Julie DeSander Head of Business Development 84
Slide 84: ~$2.5B in potential milestones & royalties; $525M already received
Agenus Notable Strategic Partnerships ~$2.5B in potential milestones & royalties; $525M already received $172.5M $10M $145M $9M $190M received1 received received2 received received Eligible Eligible Eligible Eligible Eligible • $1.7Bn milestones • $200M milestones • $450M milestones • $85M milestone
Slide 85: 2020 Partnering Strategy
2020 Partnering Strategy Ex-US Clinical Partnerships Collaborations Research Platform Collaborations Collaborations/ Collaborations /In-licensing In-licensing 86
Slide 86: Q&A
Q&A ogenus
Slide 87: ogenus
ogenus