Slide 1: August 2020
August 2020 This version of the presentation includes corrections to an error in the original presentation contained on slide 10.
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 clinical development and regulatory plans and timelines and anticipated corporate milestones. These for
Slide 3: Key Achievements in Advancing Innovative I-O Therapies
Key Achievements in Advancing Innovative I-O Therapies • Delivered 15 INDs (2016 - Present) • Generated $575M (2014 - Present) • Corporate collaborations • Produced 11 clinical batches GMP mAbs • Monetization of royalties • Positive clinical data released: • Delivered on commitments to partners • 26
Slide 4: Agenus Owned Pipeline Highlights
Agenus Owned Pipeline Highlights Mechanism/Target Product Preclinical Ph1 Ph2 Ph3 Filed Approved CTLA-4 Zalifrelimab AGEN1884 BLA filing preparations underway for Bali + Zali PD-1 Balstilimab BLA filing preparations underway AGEN2034 Multipurpose 2nd Gen CTLA-4 AGEN1181 TIGIT AGEN1327 TIGIT AGEN1777
Slide 5: PD-1 Market is Large with Ample Room for New Entrants
PD-1 Market is Large with Ample Room for New Entrants Top selling PD-(L)1 agents have a combination strategy WW PD-(L)1 Sales ($B) 2025E PD-(L)1 Sales ($B): Top Sellers are Driven by Combos 2.2x in 5 years 51.0 47.0 42.5 37.9 bo 33.1 om oc em 28.2 Ch bo 22.8 22 y com v o Yer bo 16.2 in com 13.7 s t
Slide 6: Cervical Cancer: Substantial Need for More Effective Treatments
Cervical Cancer: Substantial Need for More Effective Treatments ADVANCED CERVICAL CANCER 1st LINE TREATMENT 2nd LINE TREATMENT AGENUS OPPORTUNITY ~22,000 ~9,600 • Best available therapy (Pembro) has 14% ORR in PD-L1+ patients eligible patients eligible patients • AGEN combo is 26% ORR in all comers
Slide 7: Agenus' Balstilimab (anti-PD-1) +/- Zalifrelimab (anti-CTLA-4)
Agenus’ Balstilimab (anti-PD-1) +/- Zalifrelimab (anti-CTLA-4) Potential Best-in-class treatment for second-line cervical cancer Fast Track Designation received for Balstilimab +/- Zalifrelimab Evolution of cancer therapies Chemotherapy Roche Merck AGEN PD-1 AGEN PD-1 + CTLA-4 Topotecan1 Bevacizumab
Slide 8: Targeting CTLA-4: Best PD-1 Combination Partner
Targeting CTLA-4: Best PD-1 Combination Partner Improves Responses & Durability of responses in solid Tumor cancers Previously treated MSI-H CRC 34% 58% ORR with PD-1 alone 1L Melanoma 45% 57% ORR when CTLA-4 is added to PD-1 1L NSCLC (≥50% PD-L1) 37% 45% 1L RCC 36% 41% 2L+ Bladder cancer 21% 38% 1L
Slide 9: Balstilimab +/- Zalifrelimab: $1B+ Potential with Expanded use
Balstilimab (anti-PD-1) +/- Zalifrelimab (anti-CTLA-4): $1B+ Potential with Expanded use* US Sales of approved PD-(L)1 antibodies Top 3 indications by revenue 15 10 $B 5 0 2020 2021 2022 2023 2024 NSCLC Melanoma RCC Indication 2024 US Sales Estimate 5% Share 10% Share Non-small cell lung cancer (NSC
Slide 10: Zalifrelimab Generates Complete Responses Alone and in PD-1 Refractory Patients
Zalifrelimab (anti-CTLA-4) Generates Complete Responses Alone and in PD-1 Refractory Patients Phase I Overview • Phase 1 data demonstrated 1 CR; 4 SD • Zalifrelimab demonstrated a curative CR & durable PR in • Phase 2: monotherapy in PD-1 refractory patients refractory angiosarcoma • Preliminary dat
Slide 11: Anti-CTLA-4 +/- Anti-PD-1 Demonstrated Clinical Benefit in Cutaneous Angiosarcoma
Anti-CTLA-4 +/- Anti-PD-1 Demonstrated Clinical Benefit in Patients with Cutaneous Angiosarcoma 11 Florou, Wilky et al. Journal for ImmunoTherapy of Cancer (2019) 7:213
Slide 12: Doxorubicin + AGEN2034/1884 (anti-PD1/CTLA-4)
Doxorubicin + AGEN2034/1884 (anti-PD1/CTLA-4) Hypothesis: Doxorubicin will increase antigen presentation/T cell expansion in combination with checkpoint blockade Design: Open Label, single arm, single center, Phase II for up to 28 evaluable patients with advanced/metastatic STS, anthracycline naïve,
Slide 13: Agenus has Generated $575M from Strategic and Financial Transactions
Agenus has Generated $575M from Strategic and Financial Transactions (2014 – Present) $172.5M $35M $10M $145M $9M $205M 13
Slide 14: Agenus' next Generation I-O Innovations
Agenus’ next Generation I-O Innovations AGEN1181: Multi Functional CTLA-4 AGEN1777: First-in-class TIGIT bispecific AGEN1327: Fc-enhanced TIGIT monospecific AGENT-797: Allogeneic iNKT cell therapy
Slide 15: AGEN1181: Multifunctional anti-CTLA-4
AGEN1181: Multifunctional anti-CTLA-4 AGEN1181 is Fc enhanced ! To expand benefit to 3X more patients than first gen anti CTLA-4 ! To deliver superior performance alone and in combination with anti-PD-1 ! To improve safety Source: Agenus data 15 Waight et al., Cancer Cell 2018
Slide 16: AGEN1181 + Balstilimab: Endometrial Cancer Patient Response
AGEN1181 + Balstilimab (anti-PD-1): Endometrial Cancer Patient Shows Partial Response in Three Target Lesions and Complete Response in Non-Target Lesion Target Lesion 1 Target Lesion 2 Target Lesion 3 Non-Target Lesion Baseline 12 weeks 16 Source: Agenus data Aug 2020 Update: Patient achieved Comple
Slide 17: AGEN1181/Balstilimab Combination has Blockbuster Revenue Potential
AGEN1181/Balstilimab Combination has Blockbuster Revenue Potential Fast to market strategy via accelerated pathways in indications with large market and no active treatments Targeting cancer patients who have failed previous US Population (2020E) standard therapies for: Non-small cell lung cancer (N
Slide 18: TIGIT: Highly Promising Novel Target for Immuno-Oncology
TIGIT: Highly Promising Novel Target for Immuno-Oncology What is TIGIT? (aka T cell immunoreceptor with Ig and ITIM domains) • A critical regulator of innate and adaptive immune response • A key synergistic mechanism to anti PD-1 therapy • Hence, a natural partner for PD-1 combination therapy – part
Slide 19: AGEN1327 and AGEN1777 TIGIT Programs
AGEN1327 (TIGIT monospecific) as Optimal PD-1 Partner AGEN1777 (TIGIT bispecific) for PD-1 Refractory Tumors AGEN’s Fc-enhanced TIGIT monospecific AGEN1777 shows effective tumor control offers superior tumor control in PD-1 refractory colon cancer model Control AGEN1777 Competitor-like TIGIT mAb Ant
Slide 20: Rationale Combination Therapy with AGEN1181 Expands Therapeutic Reach
Rationale Combination Therapy with AGEN1181 Expands Therapeutic Reach and Enables Curative Responses Expanding the therapeutic potential of anti-PD-1 and anti-CTLA-4 therapy with innovative Fc engineering and rationale combinations for the treatment of solid tumors. Antoine J. Tanne, Sylvia Vincent,
Slide 21: AGEN1181: Identifying effective combinations across our pipeline
AGEN1181: Identifying effective combinations across our pipeline AGEN1181 synergizes + HSC70 Vaccine AGEN1181* + iNKT activating therapy and PD-1 to promote anti-tumor immunity clear lung metastases 300 100 Isotype Control Pulmonary Nodule Counts HSC70 vaccine + QS-21 1. Isotype Control Percent surv
Slide 22: iNKTs - Invariant Natural Killer T Cells
iNKTs - Invariant Natural Killer T Cells Unmodified allogeneic cell therapy to treat solid tumors and COVID-19 AgenTus iNKTs: IL-12 ! Require no genetic manipulation iNKT Tumor associated ! Have potential to treat both solid and liquid tumors cell macrophages GzmB/FasL ! Diminish the risk of graft v
Slide 23: Agenus
ogenus