November 2021

This presentation contains forward-looking statements that are made pursuant to the safe harbor provisions of the federal securities laws, including statements regarding Agenus’, MiNK’s, and SaponiQx’s clinical development and regulatory plans (including the scope of any regulatory approval and the ability to obtain priority review) and timelines for product candidates including balstilimab, zalifrelimab, AGEN1181, AGEN1327, AGEN1777, AGEN2373, and AGENT-797; our pipeline’s potential to meet multiple blockbuster opportunities; anticipated safety and efficacy based on the design of clinical candidates; goals for 2021 and 2022; anticipated commercial market opportunities (including partnering and licensing opportunities); our ability to collect milestone and royalty payments; our ability to continue to self-finance Agenus; our ability to develop first in class drug candidates, adjuvants, antigens and formulations, and our ability to meet manufacturing demands. These forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially. These risks and uncertainties include, among others, the factors described under the Risk Factors section of our most recent Quarterly Report on Form 10-Q or Annual Report on Form 10-K filed with the Securities and Exchange Commission and made available on our website at www.agenusbio.com. Agenus cautions investors not to place considerable reliance on the forward-looking statements contained in this presentation. These statements speak only as of the date of this presentation, and Agenus undertakes no obligation to update or revise the statements, other than to the extent required by law. All forward-looking statements are expressly qualified in their entirety by this cautionary statement

Forward-Looking Statements

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Agenus’ Comprehensive and Sustainable Business Model and Strategy

Direct product revenue & profits

Annuity income from licensed products

The Agenus Team

Supportive

Programs

Key Operational

Capabilities

• Commercial manufacturing

• Commercial readiness

• VISION research engine

Significant Value

Creators

• AGEN1181

• AGEN2373

• AGENT-797 (iNKTs)

• QS21 StimulonTM

Potential Cash

Generators

• Collaborator programs

‒ 10 clinical programs

‒ $2.8B milestones + royalties

• MiNK

• SaponiQx

• New collaborations

• Balstilimab

• Zalifrelimab

• Clinical collaborations

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* Includes AGENT-797 IND filing. **Includes $20M milestone payment that has been triggered from BMS following dosing of first patient with AGEN1777.

SHINGRIX is a registered trademark of GSK

Sustainable Ecosystem of Innovation

2020SALES~$2.7BN

Recent BMS collaboration provided

$200M upfront, up to $1.34Bn

remaining in milestones, plus royalties

SUSTAINABLE

ECOSYSTEM OF

INNOVATION

Durable and Dynamic

Research and Development

Engine

Emerging Leader in Immuno-Oncology

Unique Track Record of

Sustainable Self-Financing

$805MIN PARTNERSHIPS & TRANSACTIONS**

YRS*

17 INDsDELIVERED

IN THE PAST5Integrated R&D approach

delivers accelerated timelines

and continuous innovation

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UNPRECEDENTED EARLY

CLINICAL RESPONSES

NEXT-GEN

CTLA-4

BALSTILIMAB IN 2L CERVICAL CANCER

DIFFERENTIATED

PD-1

Significant Value Creators

AGEN1181: Next-generation Fc-enhanced CTLA-4AGENT-797: Clinical-stage Allogeneic iNKT Cell Therapy Platform (MiNK)AGEN2373: Conditionally Active CD137QS21 StimulonTM: Proven Vaccine Adjuvant (SaponiQx)

AGEN1181: Next-Generation Fc-enhanced CTLA-4 AntibodyStatus: Phase 1/2 ongoing with 100+ patients enrolled across multiple tumor types

Source: Capital IQ, El-Khoueiry et al. SITC 2021 Poster 479, Shapiro et al. AACR 2021 Poster 1677, Tanne et al. AACR 2021 Poster 1878, O’Day et al. SITC 2020 Poster 734.

• First anti-CTLA-4 antibody to demonstrate clinical activity in 9 cold, treatment-resistant tumors as

monotherapy and in combination with PD-1 (balstilimab)

• Designed to:

✓ Expand curative benefits of I-O to cold tumors that do not respond to approved immunotherapies

✓ Improve clinical benefit in hot tumors such as melanoma where I-O is effective, but not for all patients

✓ Optimize therapeutic window to reduce or eliminate side effects that influence treatment discontinuation

• Combination partner for PD-1, chemo, cell therapy, and broad range of next generation cancer therapies

• Potential for rapid path to market in hot and cold tumors supported by early clincial data

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AGEN1181 Optimizes CTLA-4 Activity for Enhanced Patient Benefit

Expanded Patient Reach

✓ Engineered to optimally engage all variants of FcyRIIIA, unlike current CTLA-4 antibodies that bind poorly to low affinity variants

✓ Expected to extend therapeutic benefit to the 40% of patients who express the low affinity FcyRIIIA receptor and are unlikely to respond to current CTLA-4 antibodies

Enhanced Potency

✓ Improves quality of the ‘immune synapse’ between T cells and APCs, boosting T cell activation, priming, and memory formation

✓ Enhances depletion of intratumoral Tregs, potent suppressors of antitumor immunity contributing to immunotherapy resistance

✓ Combination synergy potential with a range of therapies, including chemo, cell therapy, vaccines, and other checkpoint therapies

Improved Safety

✓ Avoids complement binding, mitigating difficult-to-treat side effects such as hypophysitis(no cases reported in clinic to date)

✓ Broader therapeutic index – no clinical abnormalities detected in NHP models (up to 100mg/kg)

Optimized front end

High binding affinity to CTLA-4

Fc-enhanced back

end

Improved

T cell activation,

priming, intra-tumoral

Treg depletion

7 Source: El-Khoueiry et al. SITC 2021 Poster 479, Shapiro et al. AACR 2021, Tanne et al. AACR 2021 Poster 1878, O’Day et al. SITC 2020 Poster 734, Tanne et al. AACR 2020 Poster 922

AGEN11811st generation

molecules

Conditionally active

molecules

Non-fucosylated

Bispecifics

EFFICACY

Novel Fc-mechanism promotes

better T cell priming and Treg

depletion1

SAFETY

Expected to avoid complement-

dependent irAEs

(e.g. hypophysitis)2

PATIENT REACH

Expands population 3X via improved

binding to CD16 (FcyRIIIA) for low

(F/F) & high affinity allele patients1

1Tanne et al. AACR 2020. 2O’Day et al. SITC 2020.

(e.g. ipilimumab) (e.g. BMS ProBody®) (e.g. BMS) (e.g. Macrogenics)

AGEN1181: Advantageous vs Every Competitor Class

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AGEN1181 +/- balstilimab demonstrates benefit in multiple cancers

Source: El-Khoueiry et al. SITC 2021 Poster 479.* Indicates PD-1 relapsed/refractory patient; + indicates response ongoing (data cut-off Sept 17 2021)

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• Interim readout of a Phase I dose escalation study of AGEN1181

monotherapy and combination with balstilimab included responses

across 9 cold & treatment refractory cancers (SITC 2021)

• Evidence of monotherapy activity, with four cases of confirmed

objective response

‒ First reported response to CTLA-4 monotherapy in MSS-

endometrial, pancreatic, and PD-1 refractory cervical cancer

• 17 objective responses across MSS colorectal cancer, ovarian

cancer, MSS endometrial cancer, melanoma, pancreatic cancer,

cervical cancer, visceral angiosarcoma, NSCLC, leiomyosarcoma

• Multiple responses in patients expressing the low affinity FcyRIIIA

receptor (F/F), who are unlikely to respond to 1st generation CTLA-4

• No cases of hypophysitis, pneumonitis, or high-grade hepatitis

• Phase 2/3 trials initiating in colorectal and gynecological cancers

Clinical Highlights (SITC 2021)

AGEN1181 + balstilimab benefits majority of MSS-CRC patientsInitiating Phase 2/3 study in MSS-CRC

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AGEN1181 Monotherapy

AGEN1181 + Balstilimab

Regorafenib or TAS-102

Endpoints:

ORR, DOR,

PFS, OS,

Safety,

Biomarkers

R

Phase I Data – MSS CRC Phase II/III Study Design

Target Population Unmet Need

Chemo-refractoryStandard of care options offers OS of 6-9 months and

ORR of ~2%

Source: El-Khoueiry et al. SITC 2021 Poster 479.

MSS CRC patients treated with ≥1 mg/kg AGEN1181 plus balstilimab

• 4 responses of 20 evaluable patients

• 10 stable disease

• 70% disease control rate

AGEN1181 +/- balstilimab benefits majority of GYN patientsInitiating Phase 2 study in Ovarian and MSS-Endometrial cancers

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Phase I Data – GYN Phase II Study Design

Cohort Target Population Unmet Need

OvarianPlatinum resistant /

refractory

• No effective SOC after progression on chemo

• Benefit of PARP restricted to HRD+ patients

• Alternative single-agent chemotherapies have

significant toxicity and poor clinical outcomes

MSS

Endometrial

Failure after / ineligible

for pembrolizumab +

lenvatinib

No standard of care exists

AGEN1181 Monotherapy

AGEN1181 + Balstilimab

Endpoints:

ORR, DOR,

PFS, OS,

Safety,

Biomarkers

R• 3 responses of 3 evaluable endometrial patients

• 3 responses, 2 stable disease of 9 evaluable ovarian patients

Source: El-Khoueiry et al. SITC 2021 Poster 479.

Patients with ovarian cancer treated with ≥1 mg/kg AGEN1181 plus balstilimab; MSS endometrial patients treated with monotherapy or lower combination dosing as indicated.

Curative potential with iNKT

activating cell therapy

CTLA-4 Also Complements Other Oncology MechanismsPotential to become a key backbone therapy in I-O

Curative potential in

vaccine combos

Significant tumor control with

standard of care therapies

Enhanced T cell responsiveness

in TIGIT combos

12 Source: Tanne et al. AACR 2020.

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1 Initiating Phase 2/3 studies in MSS-CRC and GYN tumors (ovarian, MSS endometrial)

2

3 Explore additional fast to market strategies in large indications with no effective therapies

Next Steps with AGEN1181Goal: Revolutionize CTLA-4 therapy

4 Pursue additional AGEN1181 combination synergies beyond PD-1

Initiating combination study with AGEN2373 (CD137 agonist) in PD-1 R/R melanoma

AGEN2373

• CD137 agonist monoclonal antibody

• Designed to be conditionally active to selectively

enhance tumor immunity while mitigating side effects

associated with systemic CD137 activation

Phase I Update

• Prolonged disease stabilization in heavily pretreated

patients with advanced solid tumors

• Good tolerability; no liver toxicity reported

• Initiating combination studies with AGEN1181 in PD-1

relapsed or refractory melanoma

Source: Tolcher et al. ASCO 2021

AGEN2373 for Optimal CD137 & FcγR TargetingStatus: Phase 1b underway

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iNKT Cells

• Distinct T cell population with rapid activation kinetics of innate immune

cells and effector functions of adaptive T cells

• Naturally promote protective immunity and limit pathological immune

activation

• Orchestrate innate and adaptive immune responses in cancer, GvHD

and infectious disease

Key Properties:

• Home to tumors and activation by CD1d and stress ligands - potent

tumor killing

• Dampen inflammatory donor T-cell activity to suppress GVHD

• Activated through CD1d to secrete pro-inflammatory cytokines to clear

infections

• Invariant T-cell receptor, no Graft versus Host Disease

• Scalable manufacturing, cost efficient

Independent allo-iNKT cell therapy company with access to Agenus’ antibodies (IPO launched Oct 2021)

• AgenT-797 demonstrated 77% survival in elderly mechanically ventilated patients with severe ARDS secondary to COVID-19*

• AgenT-797 showed early signs of tumor biomarker suppression in r/r multiple myeloma with disease stabilization for >6 months*

AGENT-797: MiNK TherapeuticsiNKT cells combine innate and adaptive immunity

Mechanism / Indication Product Preclinical Phase 1 Next Milestone

Native iNKT Cells

On

co

log

y

Solid Tumors

r/r NSCLC, SCCHN,

Metastatic Melanoma,

HCC2

AGENT-797

H1-22: Phase 1 read-out

AGENT-797+ Checkpoint Antibodies

r/r Multiple Myeloma AGENT-797 Q4-21: Phase 1 read-out

Imm

un

e

Me

dia

ted

Dis

ea

se

s GvHD AGENT-797 H2-22: Phase 1 read-out

ARDS Secondary to

COVID-19 AGENT-797 Q4-21: Phase 1 read-out

Engineered iNKT Cells

BCMA-CAR-iNKT By Q4-22: IND clearance

Stromal target-CAR-iNKT By Q4-22: IND clearance

*presented at SITC November 12, 2021

Secure Supply Chain:

Removes raw material

constraints and

heterogeneity faced by

competitors

Scalable Supply:

Scalable process designed

to meet current needs &

future pandemic threats

Comparable:

Bark and cell culture QS21

have comparable chemical

& biological properties

Cost Advantage:

Cell culture manufacturing

significantly reduces cost

of goods relative to bark

extract

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Cell Culture QS21 Stimulon™: SaponiQxProprietary manufacturing process solves today’s supply constraints with bark extract QS21

Gen1Treebark-

based

Purifying a naturalproduct

chemically extracted from a

rare tree in Chile

● Current adjuvant inShingrix™

Gen2 Cell culture-

based

Transitioning to asustainable

and highly scalable product

made with plant cell cultures,

enabled by partnership with

Phyton Biotech

● Secure supplychain with

consistent quality and scale-

able production

● Environmentally sustainable

● Improved manufacturing

Producing QS21 Stimulon™

and QS7 as well as engineered

derivatives fora new generation

of tailoredadjuvants

Gen3Foundry-based

● Tailored immune activity to

maximize therapeutic

benefit

● Expanded IP opportunities

● Improved manufacturing

Gen4High-velocity

vaccine platform

Developing a modular vaccine

platform designed to rapidly

integrate antigen, adjuvant,

and carrier into a potent

system for best-in-class

formulations against

existing, emerging, and

personalized antigens

● Pandemic threats

● Autogenous and Allogenic

Cancer Vaccines

● ChronicDisease

● InfectiousDisease

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Beyond QS21: Building an Integrated Vaccine PlatformApplying AI, automation, and biology to build portfolio of best-in-class adjuvants, antigens & formulations

Potential Cash Generators

New Collaborations

Collaborator Milestones

MiNK

SaponiQx

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• $200M upfront cash payment received

• $20M milestone payment triggered following dosing of first patient with AGEN1777

• Up to $1.34B in additional milestone payments

• Double-digit royalties up to mid-teens percent

Financials

Optionality

• Option to conduct clinical studies under the development plan

• Option to access AGEN1777 for combination studies with certain pipeline agents

• Option to co-fund a minority of global development costs for increased US royalties

up to the low-twenties percent

• Option to co-promote AGEN1777 in the US

New Collaborations: BMS Case StudyPotential first-in-class and best-in-class anti-TIGIT asset

Collaborator MilestonesEligible for up to $2.8B+ in additional milestone payments

20 * Xoma eligible to receive 10% of milestones and 33% of royalties from Merck and Incyte transactions

AGEN1777 (TIGIT bispecific)

• Up to $1.34B in aggregate milestones remaining plus double-digit royalties

AGEN2373 (CD137)

• Up to $575M in option fees and aggregate milestones remaining plus up to mid-teen royalties

INCAGN1876 (GITR), INCAGN1949 (OX40), INCAGN2390 (TIM-3), INCAGN2385 (LAG-3)

• Up to $500M in aggregate milestones remaining plus up to low double-digit royalties*

Zalifrelimab (1st gen CTLA-4) for local delivery of urinary tract cancers

• Up to $200M in aggregate milestones remaining plus up to low-twenties royalties

Balstilimab (PD-1) & zalifrelimab (1st gen CTLA-4) in Greater China

• Up to $100M in aggregate milestones remaining plus up to low-twenties royalties

MK-4830 (ILT4)

• Up to $85M in aggregate milestones remaining plus royalties*

SHINGRIX (HCR royalty monetization)

• $25.25M upon Shingrix reaching $2.75B LTM net sales any time before 2026

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• Pioneering the discovery, development and commercialization of allogeneic, off-the-

shelf, iNKT cell therapies for cancer and immune-mediated diseases

• IPO launch in October 2021 with $46M raised

• Agenus owns ~79% of total shares outstanding

• Building an innovative adjuvant platform to deliver both sustainable and secure

manufacturing approaches for saponin-based adjuvants (including QS-21 Stimulon™)

• Developing novel adjuvants and more effective formulations with optimized antigen-

adjuvant pairings

Third Party Financing: Cell Therapy & VaccinesFinancing our diversified I-O engine

Supportive Programs

Balstilimab

Zalifrelimab

Clinical Collaborations

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• 20% ORR in PD-L1 (+) patients; ~40% improvement to pembrolizumab2

• All-comers ORR of 15%, with a median duration of response of 15.4 months

Balstilimab

Monotherapy1

Balstilimab +

Zalifrelimab

• 33% ORR in PD-L1 (+) patients; 26% ORR in all-comers presented at ESMO 2021

• Expands benefit of anti-PD-1 alone

• Combination strategy update in 2H 2021

Balstilimab and Zalifrelimab in 2L Cervical Cancer

1 https://investor.agenusbio.com/news-releases/news-release-details/agenus-provides-update-balstilimab-development2 Chung HC et al., J Clin Oncol. 2019 Jun 10;37(17):1470-1478.

Advantages of Balstilimab (“Bal”) Combinations

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Bal clinical data supports a differentiated mechanism; bal+1181 combination data may offer expanded and greater performance

• Bal showed responses in 2L cervical in both PD-L1+ (20%) and PD-L1- (8%) patients (n=140); compared to pembro responses of 14% and 0% (n=77)

• Bal has been validated with its superior anti-tumor activity in PD-L1- tumors in compared to other PD-1 therapies (pembrolizumab, nivolumab)

• Bal+1181 combo is active in cancers unresponsive to I-O (MSS-CRC, MSS-endometrial, ovarian, angiosarcoma, PD-1 r/r NSCLC, leiomyosarcoma)

• Initiating dose escalation/selection with a different PD-1 will cost time and present additional risk; combo data may not be replicated with a different PD-1

Differentiation

Bal activity & commercial readiness de-risk future submissions; BLA withdrawal was due to a technicality in the AA process

• Clinical activity comparable or better than approved PD-1 agents (pembrolizumab in 2L cervical)

• Commercial ready - passed multiple FDA inspections/audits with no issues cited (no 483s)

• Robust safety database to support future BLA submissions (>400 patients and growing)

Regulatory

Bal efficacy and safety database supports combination development with other novel agents

• Our trials are designed to show the contribution of components of a novel combination within an indication

• Combinations with Bal or another PD-1 require individual contributions, regardless of whether a prior BLA exists in another indication

Clinical

Commercial

Bal will be priced to ensure combo agents (including AGEN1181) achieve premium pricing to reflect novelty and benefit

• Combination therapies are likely to require price concessions and be subject to reimbursement caps

• Pursing combinations with commercial PD-1's limit innovators’ ability to achieve premium pricing of novel agents

• Agenus’ end-to-end commercial manufacturing will ensure a scalable supply chain to meet demand and lower costs to enable our PD-1 pricing strategy

Source: El-Khoueiry et al. SITC 2021 Poster 479, Joyce et al. AACR Poster 5529, O’Malley et al. Gynecol Oncol 2021 Nov; 163(2): 274-280

Clinical CollaborationsExpanding balstilimab & zalifrelimab potential through partner combinations

Collaboration model enables evaluation of balstilimab and zalifrelimab in new indications

and combinations through clinical collaborations with partners

Existing collaborations include:

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Balstilimab + EP4 antagonist (CR6086)

in advanced MSS-CRC

Zalifrelimab + hedgehog inhibitor (NLM-001) + chemo

in 1L advanced Pancreatic Cancer

Key Operational Capabilities

Commercial Manufacturing

Commercial Readiness

VISION Research Engine

Commercial ManufacturingA practical asset enabling fast-to-market products

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• Clinical GMP facility acquired from XOMA Inc. in 2015

• Team of 70 scientists, engineers, technologists who have developed >20 antibody candidates

• Record speed in advancing from research cell bank to GMP in ~4 months (vs. industry average 12-18 months)

Berkeley, CA

Emeryville, CA

• Commercial GMP facility under construction

• Designed for fully integrated biologics cGMP and commercial production, including drug substance

manufacturing, drug product fill/finish, packaging and distribution under one roof

Vacaville, CA

• Greenfield site designed for commercial manufacturing expansion for internal pipeline of biologics, cell

therapy, adjuvants and beyond

• Designed to support our own programs as well as manufacturing for collaboration / partnered programs

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Clinical Trials

• Preclinical biomarkers

• Drug discovery

• Discovery screens

• Program strategy

• Competitive landscape

• Partnerships

• Collaborations

• Patient characteristics

• Clinical outcomes

• Clinical biomarkersVISION platform

Data Lake

AGEN proprietary data AGEN proprietary dataExternal data

VISION Research EngineActive learning and prediction across R&D to uncover the biology behind clinical responses

Discovery & preclinical development

Target Evaluation

• Patient selection

• Response biomarkers

• Probability of

Success models

Rational portfolio design • Optimized molecules

• Empirical combinations

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Milestones & Pipeline

✓ Bal mono met clinical endpoints in 2L cervical cancer

✓ Updated Bal/Zal combo data presented at ESMO

✓ MiNK-initiated iNKT Phase 1 cancer program*

✓ BMS collaboration on AGEN1777 ($200M upfront)

✓ AGEN1777 Phase I initiated ($20M milestone)

✓ Additional Ph I data for AGEN1181 at SITC

✓ Initial Ph1 data for iNKTs at SITC*

Completed Milestones Near-Term Milestones

• 2021: Bal/Zal combo strategy update

• 2021: Initiate AGEN1181/AGEN2373 melanoma Phase Ib

• 2022: Commence AGEN1181 Phase 2/3 trials

• 2022: File IND for novel program

• 2022: Launch Expanded Access Programs

Key Operational Milestones Update

30 * MiNK Therapeutics

Mechanism/Target Product Partner Preclinical Phase 1 Phase 2 Phase 3 Filed Approved

PD-1 Balstilimab

CTLA-4 Zalifrelimab

Next-generation CTLA-4 AGEN1181

TME Conditioning anti CD73 / TGFb TRAP AGEN1423

CD137 AGEN2373

TIGIT AGEN1327

TAM AGEN1571

Stromal targeting

Myeloid targeting

Glioblastoma (newly diagnosed) ProphageTM

Personalized Neoantigen Vaccine AutoSynVaxTM

Off-the-Shelf Neoantigen Vaccine PhosphoSynVaxTM

Allogeneic Cell Therapy – Cancer AGENT-797*

Allogeneic Cell Therapy – COVID 19 AGENT-797*

Allogeneic Cell Therapy Multiple CAR/TCRs*

TIGIT (bispecific) AGEN1777

GITR INCAGN1876

OX40 INCAGN1949

TIM-3 INCAGN2390

LAG-3 INCAGN2385

ILT4 MK-4830

Shingles & Malaria QS-21 StimulonTM

Notes: Balstilmab and zalifrelimab are being evaluated in 2L cervical cancer and undisclosed tumors. | Recepta Biopharma S.A. has exclusive rights to balstilimab and

zalifrelimab in Brazil and five other South American countries. | Malaria vaccine in development with GSK is currently filed for approval.

*MiNK Therapeutics is an affiliate of Agenus Inc.

Fully

Owned

Pipeline

Partnered

Pipeline

Fully-owned

Partnered

Program type

Option to Gilead

GreaterChina

Positioned to Lead in I-ODiverse portfolio targeting multiple aspects of the cancer immunity cycle

GreaterChina

31