8-K

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

FORM 8-K

CURRENT REPORT

Pursuant to Section 13 or 15(d)

of The Securities Exchange Act of 1934

Date of Report (Date of earliest event reported): May 14, 2015

AGENUS INC.

(Exact name of registrant as specified in its charter)

DELAWARE	000-29089	06-1562417
(State or other jurisdiction of incorporation)	(Commission File Number)	(IRS Employer Identification No.)

3 Forbes Road Lexington, MA	02421
(Address of principal executive offices)	(Zip Code)

Registrant’s telephone number, including area code: 781-674-4400

N/A

(Former name or former address, if changed since last report.)

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instruction A.2. below):

¨ Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

¨ Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

¨ Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

¨ Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Item 7.01 Regulation FD Disclosure.

Agenus Inc. (“Agenus”) is presenting a corporate slide presentation on May 14, 2015 at its Research and Development Day event in New York City. A copy of this slide presentation, dated May 14, 2015, is attached as Exhibit 99.1 to this Current Report on Form 8-K.

The information responsive to Item 7.01 of this Form 8-K and Exhibit 99.1 hereto shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934 (the “Exchange Act”) or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933 or the Exchange Act, except as expressly set forth by specific reference in such a filing.

Item 8.01 Other Events.

On May 14, 2015, Agenus issued a press release titled, “Agenus Announces Oral Presentation at ASCO Highlighting Improved Survival with Prophage Immunotherapy in Brain Cancer Compared to Historical Controls” (the “Press Release”). A copy of the Press Release is attached as Exhibit 99.2 to this Current Report on Form 8-K and is incorporated herein by reference.

Item 9.01 Financial Statements and Exhibits.

(d) Exhibits

Exhibit No.	Description of Exhibit
99.1	Presentation dated May 14, 2015.
99.2	Press Release dated May 14, 2015.

SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

Date: May 14, 2015	AGENUS INC.
	By:	/s/ Christine M. Klaskin
		Christine M. Klaskin
		VP, Finance

EXHIBIT INDEX

Exhibit No.	Description of Exhibit
99.1	Presentation dated May 14, 2015.
99.2	Press Release dated May 14, 2015.

EX-99.1

Exhibit 99.1

Agenus R&D Day May 14th 2015

Driving the immune a system to fight cancer and infectious disease

Note Regarding 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 Quarterly Report on form 10-Q filed with the Securities and Exchange Commission on May 1, 2015 and made available on our website at www.agenusbio.com. When evaluating Agenus’ business and prospects, careful consideration should be given to these risks and uncertainties. These statements speak only as of the date of this presentation, and Agenus undertakes no obligation to update or revise these statements. This presentation and the information contained herein do not constitute an offer or solicitation of an offer for sale of any securities.

2

Introduction Garo Armen, PhD

Immuno-Oncology Overview Bob Stein, MD, PhD

Tumor Recognition John Castle, PhD

Glioblastoma (GBM) Orin Bloch, MD—NW U

Agenus / 4-Antibody Robert Burns, PhD

Monoclonal Antibodies Marc van Dijk, PhD

Checkpoint Modulators (CPMs) Nicholas Wilson, PhD

Combination Immunotherapy Charles Drake, MD—JHU

Science Wrap-up Bob Stein, MD, PhD

Discussion – Q&A All

Closing Remarks Garo Armen, PhD

Three Synergistic Immune-Modulating Platform

Poised to Create Best-in-Class Immunotherapies

+ Ph 2 in ndGBM

+ Ph 2 w HerpV

Heat Shock Protein-Based Vaccines

QS-21 Checkpoint Stimulon® Modulators

+ Ph 3 Malaria Adjuvant (CPMs)

+ Ph 3 Shingles

4

Merck/Agenus CPM Collaboration: Focus on Oncology

Established April 2014

Uses Agenus’ monoclonal antibody platform

Two undisclosed targets

Financial considerations

Merck pays all R&D costs

Up to $100 MM milestones per successful compound Mid-single digit royalties

5

Incyte/Agenus Immuno-Oncology Collaboration

Established February 2015 Initial focus on 4 CPM targets:

– GITR and OX40 agonists

– TIM-3 and LAG-3 antagonists

Financial considerations

$60M upfront (with equity investment) Up to $350M in milestones for lead programs

Royalty bearing products (TIM-3, LAG-3): 6%-12% royalty rate 50:50 cost and profit share programs (GITR, OX40)

6

Agenus Pipeline

Partnered Not Partnered

7

QS-21 Stimulon® Saponin Adjuvant

Generates strong antibody and cell-mediated immune responses Safe & well tolerated in >50,000 people

8

Robust Phase 3 Results with Shingles Vaccine

GSK Merck

Efficacy: 97% 50-70%

1 out of 3 people will get shingles in their lifetime

Target population: 370M

9

R&D Day

Introduction Garo Armen, PhD

Immuno-Oncology Overview Bob Stein, MD, PhD

Tumor Recognition John Castle, PhD

Glioblastoma (GBM) Orin Bloch, MD—NW U

Agenus / 4-Antibody Robert Burns, PhD

Monoclonal Antibodies Marc van Dijk, PhD

Checkpoint Modulators (CPMs) Nicholas Wilson, PhD

Combination Immunotherapy Charles Drake, MD—JHU

Science Wrap-up Bob Stein, MD, PhD

Discussion – Q&A All

Closing Remarks Garo Armen, PhD

The Immune System… defends from enemies from without

11

The Immune System… defends from enemies from without & within

12

Immunological Surveillance

Macfarland Burnet (1957): “It is by no means inconceivable that small accumulations of tumour cells may develop and because of their possession of new antigenic potentialities provide an effective immunological reaction with regression of this tumor and no clinical hint of its existence.”

13

Accumulated Mutations Drive Cancers

Various carcinogens (sun, smoke, gamma

Approximately 1% rays, etc.) of mutations produce stochastic produce mutant mutations proteins (<0.03% of genome)

A handful hit growth- A fraction of these related genes, driving produce potential T-cell malignancy neo-epitopes – potential (5-10) basis for immune rejection (1-20+)

14

Cancer- In Limbo between Self & Non-Self

Mutational Heterogeneity in Cancer

Taking off brakes may be enough

May need agonists, Unclear how widely vaccines, adjuvants, etc.

Immuno-Rx will work

Lawrence MS et al. Nature 2013; 499: 214-18

100 mutations per Mbase = 0.01% of genome

15

Agenus R&D Day

Heat-Shock-Protein (HSP)-based Vaccines

A strategy for Tumor-Specific Immuno-education

Pre-Clinical Overview

The Immune System Can Defeat Cancer

The Observations that led to Agenus

TUMOR A TUMOR A or B CELLS INJECTED CELLS INJECTED

Tumor mass is resected

from mouse Mouse cured of tumor A immune to tumor A

Naïve mouse Mouse forms Mouse Cured tumor mass Of Tumor A

Mouse cured of

Requires immune system tumor A NOT

immune

Requires T Cells & NK Cells to tumor B

Mouse Cured

Of Tumor A

Adapted from Srivastava 2002 Ann Rev Immunol 20:395

17

Immunity is Individually Tumor Specific

10 different methylcolanthrene-induced murine fibrosarcomas

Tumors Used to Immunize

A BB C C D D E E FF G H H I I J A A + — — — — -

e

ng B B—+ — — — —

l e C

C — + — — — -

al

Ch D D ——+ — — —to E E — — + — — -Used F F — ——+ — —

G

rs G — — — + —

o H

m H — — ——+ —

u

T II — — — — + -J J — — — ——+

Basombrio 1970 Cancer Res. 30:2458

18

Heat Shock Protein Fractions Confer Immunity

hsp70 hsp90 hsp110 gp96 grp170

CRT

Tumor cell Proteins liberated Proteins tested in Heat Shock Proteins (HSP) from tumor cell tumor rejection assays elicit anti-cancer immunity

Tumor

Rx Rx

Challenge

Tumor DAY 0 7 14 size

MONITOR TUMOR GROWTH Days post tumor

challenge

19

Heat Shock Proteins (HSPs)

Quality Control for the Intracellular Proteome

Cellular Peptides Chaperoning by HSPs

Mutated / Normal

Abundant class of intracellular proteins Constantly sample intracellular proteome Sense and manage misfolded proteins Natural role in immune recognition of damaged cells, non-self antigens

20

Prophage Mechanism of Action

Cell

D8+ T Cell

IL-12 NK Cell

TNF? MCP-1 IL-1?

MIP-1á

GM-CSF

RANTES NO

Modified from

21

Heat-Shock-Protein (HSP)-based Vaccines

Personalized Immuno-education

Clinical Overview

Agenus R&D Day

Prophage confers tumor-specific immunity

Tumor Heat Shock Protein bound tumor antigens

Prophage

Intradermal injection

23

Prophage: Sporadic Efficacy in Previous Studies

Patient remains disease-free at 10+ years

Before 16 Months 32 Months Prophage Post-Treatment Post-Treatment

Belli F et al., J Clin Oncol 2002;20:4169-4180

24

Prophage Clinical Summary

Autologous Cancer Vaccine Practical logistics Cost-effective manufacture Pharmaceutically tractable Well-tolerated

Promising efficacy signal in newly diagnosed GBM Phase 3 ready program with near-term registration opportunity Potential synergy with CPMs

25

R&D Day

Introduction Garo Armen, PhD Immuno-Oncology Overview Bob Stein, MD, PhD

Tumor Recognition John Castle, PhD

Glioblastoma (GBM) Orin Bloch, MD—NW U Agenus / 4-Antibody Robert Burns, PhD Monoclonal Antibodies Marc van Dijk, PhD Checkpoint Modulators (CPMs) Nicholas Wilson, PhD Combination Immunotherapy Charles Drake, MD—JHU Science Wrap-up Bob Stein, MD, PhD Discussion – Q&A All Closing Remarks Garo Armen, PhD

Agenus R&D Day

Immunological Recognition and Rejection of Tumors

The genetic basis of patient-specific immunity

Next-Generation Sequencing (NGS)

Tumor DNA sequence data

28

Next-Generation Sequencing (NGS)

Tumor DNA sequence data

Terabytes of data

29

Next-Generation Sequencing (NGS)

Tumor DNA sequence data

Terabytes of data

EFKHIKAFDRTFANNPGPMVVFATPGM Protein-changing EFKHIKAFDRTFADNPGPMVVFATPGM mutations

30

Genome Sequencing Costs Have Plummeted!

The first human genome cost $3 billion and took 10 years. A genome can now be sequenced in one week for $3 thousand

31

We Can Now Determine Tumor Genomes

Reoccurring tumor mutation

Genes Patient tumors

Each dot is a tumor mutation

Patient-specific tumor mutations

PJ Stephens et al. Nature, 1-5 (2012)

32

Tumors Typically Have 10 To 500 Protein-changing Mutations

a m a e o m l l b a l l c o e m r n c o e a i h i o l c s c s p l l y o k r u og e r n c a o e c a a l i e c m r m l l a c o m o d i i rn n a r a a o p r a a h r l e t a t c s l d h e u d g n t e l s e a a n c r d q m i tc ac ap e e m a e a s o o s l r i a t a n l l l m n r n u i c a d n r a a e r s e a b a o r i c o t v d m g g a L y n w a r n o n d n l c r a d n n l M r e e v o d e l i e t e o e e e o l a e h o r n a t u u A T B R L O P A R G R E U P C R C H S B L L M

1000

750

Mutated Mutated

500

proteins proteins

250

0

9 14 28 29 33 39 39 43 47 51 52 52 57 67 73 78 92 99 123 163 183 215 266

Median per tumor

J. Castle, Agenus proprietary analysis of TCGA tumor profiles

33

Tumor Mutations

Tumors typically have between 10 and 500 protein mutations Over 98% mutations are unique to the specific tumor

DNA Tumor cells mutations

34

Tumor Mutations

Tumors typically have between 10 and 500 protein mutations Over 98% mutations are unique to the specific tumor

Identify immunogenic mutations

DNA Tumor cells mutations

35

How Can The Immune System “See” Mutations?

Many challenges to become an effective neo-antigen

DNA mutation in protein Transcribed to RNA Translated to protein Processed by proteasomes Transported to the ER Loaded onto MHCs (must fit) Transported to the cell surface

Stay on patient’s MHCs Be sufficiently “non-self”

Be recognized by a TCR that has not been deleted or tolerized

36

Cells Displaying Neo-antigens Recognized as Non-self by CD8+ T Cells Can Be Destroyed

37

Immunogenic Mutations in Patients

GBM patient 020-002 GBM patient 020-006

HLA types HLA types

HLA-A*02:01 HLA-A*29:02 HLA-B*35:03 HLA-B*44:03 HLA-C*16:01

HLA-A*01:01 HLA-A*68:01 HLA-B*37:01 HLA-B*51:01 HLA-C*06:02 HLA-C*15:02

Mutations

101 protein mutations

50 expressed

23 HLA presented (immunogenic)

Mutations

127 protein mutations

50 expressed

27 HLA presented (immunogenic)

38

Tumors With Many Immunogenic Mutations Respond to Inhibitory CPMs Like anti-PD-1 and anti-CTLA-4

Predict response to CTLA4 & PD1 therapies

Identify immunogenic mutations

DNA Tumor cells mutations

39

Tumors With Many Immunogenic Mutations Respond to Inhibitory CPMs Like anti-PD-1 and anti-CTLA-4

Predict response to CTLA4 & PD1 therapies

Identify immunogenic mutations

DNA Tumor cells mutations

Mutant Protein Vaccination For Patients With Fewer Immunogenic Mutations

Predict response Use mutant to CTLA4 & PD1

proteins for therapies vaccination

Identify immunogenic muteins

DNA Tumor cells mutations

41

Mutant Peptide Vaccination

Melanoma 563 expressed 50 of 50 B16F10 cells missense confirmed mutations

Exploiting the Mutanome for Tumor Vaccination Castle et al., 2013

42

Mutant Peptide Vaccination

Melanoma 563 expressed 50 of 50 Immunize with B16F10 cells missense confirmed mutation peptide mutations

Exploiting the Mutanome for Tumor Vaccination Castle et al., 2013

43

Mutant Peptide Vaccination

ELISPOT Wild type & mutated

16 of 50 mutations immunogenic

Melanoma 563 expressed 50 of 50 Immunize with B16F10 cells missense confirmed mutation peptide mutations

Exploiting the Mutanome for Tumor Vaccination

Castle et al., 2013

44

Mutant Peptide Vaccination

ELISPOT Wild type & mutated

16 of 50 mutations immunogenic

Melanoma 563 expressed 50 of 50 Immunize with B16F10 cells missense confirmed mutation peptide

mutations Tumor challenge

40% mice survive

Exploiting the Mutanome for Tumor Vaccination

Castle et al., 2013

45

Humans and Tumors Are Unique

The immune system recognizes mutated proteins

Tumors harbor a unique set of mutations

Mutated proteins are recognized by HSPs

Prophage vaccines target tumor- and patient-specific mutations

46

HSP-based Vaccines Target Multiple Mutations And Function As Personalized, Patient-specific Immunotherapies

Prophage

Patient individualized tumor vaccine

Purify heat-shock proteins (HSPs) complexed with muteins

47

Benefits

Prophage inherently captures the individuality of tumors and patients

By understanding the process, we:

Identify patients who will respond to our therapies Enable immuno-monitoring of patients in our clinical trials Can synthesize fully recombinant individualized vaccines

Identify immunogenic mutations

DNA Tumor cells mutations

48

R&D Day

Introduction Garo Armen, PhD Immuno-Oncology Overview Bob Stein, MD, PhD Tumor Recognition John Castle, PhD Glioblastoma (GBM) Orin Bloch, MD—NW U

Agenus / 4-Antibody Robert Burns, PhD

Monoclonal Antibodies Marc van Dijk, PhD Checkpoint Modulators (CPMs) Nicholas Wilson, PhD Combination Immunotherapy Charles Drake, MD—JHU Science Wrap-up Bob Stein, MD, PhD Discussion – Q&A All Closing Remarks Garo Armen, PhD

R&D Day

Introduction Garo Armen, PhD Immuno-Oncology Overview Bob Stein, MD, PhD Tumor Recognition John Castle, PhD Glioblastoma (GBM) Orin Bloch, MD—NW U Agenus / 4-Antibody Robert Burns, PhD

Monoclonal Antibodies Marc van Dijk, PhD

Checkpoint Modulators (CPMs) Nicholas Wilson, PhD Combination Immunotherapy Charles Drake, MD—JHU Science Wrap-up Bob Stein, MD, PhD Discussion – Q&A All Closing Remarks Garo Armen, PhD

Agenus Integrated Antibody Discovery Dedicated to Making Best in Class Antibody Drugs

Target Retrocyte Display™ Yeast Display (SECANT®) Phage Display

Fully human repertoire Display of full length IgG through ScFv or Fab format binding displayed on mouse pre-B cells biotin attachment Massive diversity >1010

109 Antibody library 5x109 Antibody library Differentiated screening options

Fc-engineering Computational Biology

Effector Modulation of effector functions Bioinformatics

Functions DuoBody® bi-specific technology Integrating structure and function data to understand MOA; Structure-guided optimization; Epitope analysis

Immuno-Biology Development

MOA / Immunological assays can Expertise be leveraged across Extensive internal Product multiple TAs to and used to development expertise determine appropriate isotype formats for product development

Currently accessed through CRO

Key components profiled

51

Key Components – Retrocyte Display™

Retroviral transduction of human heavy and light chain antibody genes

huIgG VH

á

â Ig

——Ig -Ig Igá â

Mouse pre-B cells huIgG

Multi- Top Leads VL Natural folding, parameter pairing, and Fully human high screening anchoring diversity stable methods antibody libraries

Iterations to identify high quality lead

52

Key Components – SECANT® Yeast Display

Biotinylated antibody is secreted and captured by the avidin on the surface of the same cell

Biotin Ligase

53

Key Components – SECANT® Yeast Display

A library of yeast cells displaying captured antibodies is exposed to fluorescently labeled target antigen. Yeast cells displaying an antibody recognizing the target are isolated by FACS

Multiple parameter

FACS selection

54

Key Components – SECANT® Yeast Display

After selection by FACS the isolated yeast cell will continue to grow, causing avidin to progressively disappear and antibody to be released into the medium

Biotin Ligase

55

Key Components – Phage Display

Phage Display Highlights

Use of VH and VL gene repertoires in well-established • Workhorse technology phage-display screening cycle • Very large libraries to provide maximum diversity

Flexible selection conditions (pH, temperature)

Primary utility generation of hit panel

ScFv or Fab format

Currently accessed through CRO

56

Key Components – Bi-specific Format

Mix & screen technology, product-ready format

Single-point mutant, homodimeric formats expressed and mixed under permissive conditions allows recombination into bi-specific formats with high efficiency

Application

combinations are key in immuno-oncology Generates new MoA

Next generation compounds

57

Modular Platform Components Interchangeable and Complementary

Key Antibody Discovery Deployable Agenus Platform Objective Process Steps Components

Lead Retrocyte SECANT® Speed & Phage Display Generation Display™ Yeast Display Diversity

Retrocyte Efficacy, Lead Fc Engineering Differentiation Display™ Optimization Developability

Candidate Cell line & CMC

Development Product development Validation

Product Development

58

Agenus Integrated Discovery Platform

Retrocyte Display™ Yeast Display (SECANT®) Phage Display

Fully human repertoire Display of full length IgG through ScFv or Fab format displayed on mouse pre-B cells biotin attachment Massive diversity >1010

109 Antibody library 5x109 Antibody library Differentiated screening options

Fc-engineering Computational Biology

Modulation of effector functions Bioinformatics

DuoBody® bi-specific technology Library design; Integrating structure (Genmab research License) and function data to understand MOA; Structure-guided optimization; Epitope analysis

Immuno-Biology Development

Immunological assays can Expertise be leveraged across Extensive internal multiple TAs to and used to development expertise determine appropriate isotype formats for product development

Currently accessed through CRO

59

R&D Day

Introduction Garo Armen, PhD Immuno-Oncology Overview Bob Stein, MD, PhD Tumor Recognition John Castle, PhD Glioblastoma (GBM) Orin Bloch, MD—NW U Agenus / 4-Antibody Robert Burns, PhD Monoclonal Antibodies Marc van Dijk, PhD

Checkpoint Modulators (CPMs) Nicholas Wilson, PhD

Combination Immunotherapy Charles Drake, MD—JHU Science Wrap-up Bob Stein, MD, PhD Discussion – Q&A All Closing Remarks Garo Armen, PhD

Targets Across the Spectrum of Tumor Immunity

Equipped to treat a range of human cancers

Modified Chen et al., 2013

*Anti-OX40

*Anti-GITR

*Anti-TIM-3 *Anti-LAG-3

Novel Platforms

Vaccine

Platforms Anti-PD1

Anti-CTLA-4

Partnered with INCY: GITR, OX40 agonist antibodies and TIM3, LAG3 antagonist antibodies

61

Antibody Discovery at Agenus

Antibody Discovery Platforms Key Filters: Examples:

Target Binding Recombinant proteins, cell lines (over-expressing, endogenous) Species cross-reactivity Human/NHP/rodent Many Hits Target selectivity Related family members

(100s+)

CDR diversity from panning Sequencing (NGS)

Blocking/non-blocking Flow cytometry (cell lines), recombinant proteins (Luminex)

Cross-competition/Affinity Reference antibodies (Flow cytometry

(EC50), affinity (SPR)) Functional evaluation Reporter gene assay(s)

Mechanistic evaluation Primary human/NHP functional assays

Developability assessment Tm, pI, yield, aggregation, IP, immunogenicity risk, PTM evaluation/stress test etc…

62

Antibodies Are Naturally Bifunctional

Variable region defines interaction with target antigen IgG Fc region dictates half-life, antibody dependent cellular cytotoxicity (ADCC), CDC, phagocytosis (ADCP)…

Activating Inhibitory Activating

Modified: Pietersz et al., Nature Review Drug Discovery 2012

63

Two Functionally Distinct Classes Of Fc? Receptors: Activating And Inhibitory

Example: Rituxan

Clynes et al., Nat Med 2000

Nimmerjahn and Ravetch Nat. Rev. Imm. 2008

64

Inhibitory Fc?RIIB Mediates Receptor Forward Signaling By Anti-TNFR Antibodies

Cross-linking (Forward signaling)

E.g: Anti-CD40/DR5

Wilson NS et al., Cancer Cell, 2011 Li et al., Science 2011 White et al., JI 2011

Nimmerjahn and Ravetch Nat. Rev. Imm. 2008

65

Canonical View of GITR Forward Signaling in T Cells

Naïve GITR -L

T cell

GITR expression

upregulated

Initial 24-72 hrs

priming

Activated

mature DC

No GITR

stimulus GITR

Secondary engagement

expansion

Effector phase

Reduced T cell Enhanced effector T cell

expansion/survival expansion/survival

Decreased Increased proinflammatory

cytokine production cytokine production

Adapted from: Current Opinion in Immunology 2012

66

Model for GITR Agonist Immunotherapy of Cancer

Cohen & Schaer et al. PloS ONE 2010 May 3;5(5) Schaer et al. Cancer Immunology Research 2013 Nov 5

Schaer, Murphy & Wolchok Current Opinion in Immunology 2012, 24:217–224

67

Fc? Receptors Contribute To The Activity Of Antibodies Targeting Immune Regulatory Molecules

TNFRs

?

Modified: Mellman et al., Nature 2011 Modified: Pietersz et al., Nature Review Drug Discov 2012

Partnered with INCY: GITR, OX40 agonist antibodies and TIM3, LAG3 antagonist antibodies

68

Preclinical: Anti-OX40 (OX86) and Anti-GITR (DTA-1) Require Intact Fc?R Interactions to Exert Anti-Tumor Activity In Vivo

Colon26 model Control DTA-1 mIgG2a DTA-1 (N297A)

700 700 700 600 600 600

3 )

(mm 500 500 500

Anti-GITR

400 400 400

Volume 300 300 300 200 200 200 100 100 100

0 0 0

0 3 6 9 12151821 0 3 6 9 12151821 0 3 6 9 12151821

Control OX86 mIgG2a OX86 (N297A)

700 700 700 600 600 600

)

3 500 500 500

Anti-OX40 (mm

400 400 400

Volume 300 300 300 200 200 200 100 100 100

0 0 0 Bulliard et al., JEM 2013

0 3 6 9 12151821 0 3 6 9 12151821 Bulliard et al., ICB 2014

0 3 6 9 12151821

Days

69

Old Paradigm: Activating Fc?Rs Enhance Cytotoxic Antibodies, Inhibitory Fc?RIIB Facilitates Antibody-Mediated Forward Signaling

Anti-CD20 Anti-CD40 Anti-EGFR Anti-DR4 Anti-Her2 Anti-DR5

Anti-FGFR3 Anti-CD27 Anti-CD19 Anti-CD30

Other… Anti-CD95

Modified from: Nimmerjahn F and Ravetch, J Cancer Immunol. 2012

70

Activating Fc?Rs Are Required for Anti-tumor Activity of Agonist GITR and OX40 Antibodies

Anti-GITR Anti-OX40 Bulliard et al., JEM 2013

Colon26 tumor model

Bulliard et al., ICB 2014

Control

Wild type

100% CR

GITR and OX40 Are Expressed By Multiple Immune Cell Subsets Within The Tumor Microenvironment

Croft et al., Ann. Rev. of Immunol. 2010 Restifo et al., Cancer Res 2012

Cell type GITR OX40

B cells ++ +/- Naive CD4 T cells +—Naive CD8 T cells +—Regulatory T cells ++++ +++ Activated CD4 T cells +++ ++ Activated CD8 T cells +++ ++ Macrophages +—NK cells ++ + NK T cells ++ + DCs (lymphoid/myeloid) -/+—Monocytes/Macrophages ++—

Granulocytes/Neutrophils—+/-

Colon26 —

Qualitative summary only. Differences in human and mouse expression are not accounted for.

72

Intra-Tumoral Regulatory T Cells Express High Levels of GITR and OX40. Antibody Treatment Leads to Depletion

Bulliard et al., JEM 2013 Colon26 model Bulliard et al., ICB 2014

GITR expression OX40 expression

Tregs

Tregs

73

Preclinical: Selective Intratumoral Treg Depletion is Rapid, and Requires Fc?R Co-engagement

Colon26 model Kinetics of Tregs depletion (within the tumor)

7.0

Control

CD4+ 6.0 DTA-1 mIgG2a

Tumor

5.0 DTA-1 N297A

FoxP3+ cells 4.0

T

of 3.0

node

2.0 28-fold

Lymph Density 1.0

0.0

0 1 2 3 4 5 6

Days post-treatment

Bulliard et al., JEM 2013

Bulliard et al., ICB 2014

Comparable results obtained with anti-OX40 surrogate antibody (clone OX86)

74

Translation to Human Tumors:

Intratumoral Regulatory T Cells Overexpress OX40

Mouse Healthy Donor Tumor Colon tumor model (CT26) PBMCs TILs

Tconv Treg Tconv Treg

A D B E C F

Bulliard Y et al., JEM 2013 Waight et al., Agenus unpublished data

75

Antibody Co-Engagement of Fc?Rs Depletes Intra-Tumoral Regulatory T Cells (Examples: GITR & OX40)

GITR & OX40 agonist antibodies deplete intratumoral Tregs Smyth M. et al., ICB 2014 Bulliard Y. et al., ICB 2014 Bulliard Y. et al., JEM 2013 Simpson et al., JEM 2013

Shelby et al., Can. Immunol. Res. 2013

GITR & OX40 agonist

GITR & OX40 agonist antibodies promote antibodies drive Teff Teff resistance to activation/expansion Treg suppression

76

Targets Across the Spectrum of Tumor Immunity

Equipped to treat a range of human cancers

Modified Chen et al., 2013

*Anti-OX40 *Anti-GITR

*Anti-TIM-3 *Anti-LAG-3

Novel Platforms

Vaccine

Platforms Anti-PD1

Anti-CTLA-4

Partnered with INCY: GITR, OX40 agonist antibodies and TIM3, LAG3 antagonist antibodies

77

Clinical Candidate: Anti-GITR Agonist Antibody (Planned IND 2015)

Goal: Differentiated mechanism of action for best-in-class potential

Example: Enhanced poly-functional T cell response by GITR agonism

Donor ID#XXXX Isotype

CD4+ 3% 3% 0% 1% T cells

12% 2%

10% 11% 3% 3% CD8+ T cells

ã

IFN

12% 5%

Reference: Agenus unpublished data

78

Clinical Candidate: Anti-OX40 Agonist Antibody (Planned IND 2016)

Goal: Differentiated mechanism of action for best-in-class potential

Example: Anti-OX40 antibody-mediated T cell modulation

n 8 i o nduct 6

I e i n 4 k o Cyt 2 ld o 0 F

y e12 s d p b b u o t y A A n i b o f f e t s e e g n I A a R R o

N Reference: Agenus unpublished data

79

Generating High-quality Antibodies is a Great Start Understanding the Target Biology is also Critical (e.g., TIM-3)

Complex biology Preclinical data

?

Days post tumor implantation

Sakuishi K et al. JEM 2010

The complexity is both a challenge and an opportunity!

80

Checkpoints – The Beginning of Understanding

B7-1/CD80 4-1BB/CD137 TIM3 2B4/CD244/SLAMF4 B7-2/CD86 4-1BB Ligand GAL-9 BLAME/SLAMF8 B7-H1/PD-L1 CD27 CD2 CD2

B7-H2/B7RP1/ICOS-L CD27 Ligand/CD70 CD7 CD2F-10/SLAMF9 B7-H3 CD30 CD53 CD48/SLAMF2 B7-H4 CD30 Ligand CD82/Kai-1 CD58/LFA-3 B7-H5/VISTA CD40 CD90/Thy1 CD84/SLAMF5 CD28 CD40 Ligand CD96 CD229/SLAMF3 ICOS HVEM CD160 CRACC/SLAMF7 PD-L2/B7-DC LIGHT CD200 NTB-A/SLAMF6 PDCD6 DR3 OX-2R (CD200R) SLAM/CD150 B7-H6 TNF-alpha CD300a/LMIR1Integrin alpha 4 beta 1 B7-H7 TNF-beta CRTAM Integrin alpha 4 beta 7/LPAM-1 BTLA (CD272) TNF RII DAP12 TCL1A

KIRs BAFF/BLyS Dectin-1/CLEC7A TCL1B

DNAM-1 (CD226) BAFF R DPPIV/CD26 TIM-1/KIM-1/HAVCR VSIG4 RELT EphB6 TIM-4 CD31 (PECAM-1) TACI HLA-DR TSLP

PILR-? (FDF03)TL1A Ikaros TSLP R

PILR-? TNRFSF25 Integrin alpha 4/CD49d A2AR

SIRP? TIGIT ( WUCAM, Vstm3) Siglec-5 (CD170) RNF125/TRAC-1 CD47 CD155 Siglec-7 (CD328) CD5 LAIR-1 (CD305) CEACAM1 (CD66a) ILT2 MAFA

BT3.1 CD33 ILT4 NKG2A

BT3.2 EP4 (PGE2 receptor) EP2 (PGE2 receptor) NKG2B BT3.3 NKG2D

Over 100 potential checkpoint proteins

AGENUS HAS ADDITIONAL UNDISCLOSED CPM PROGRAMS

81

R&D Day

Introduction Garo Armen, PhD Immuno-Oncology Overview Bob Stein, MD, PhD Tumor Recognition John Castle, PhD Glioblastoma (GBM) Orin Bloch, MD—NW U Agenus / 4-Antibody Robert Burns, PhD Monoclonal Antibodies Marc van Dijk, PhD Checkpoint Modulators (CPMs) Nicholas Wilson, PhD Combination Immunotherapy Charles Drake, MD—JHU

Science Wrap-up Bob Stein, MD, PhD

Discussion – Q&A All

Closing Remarks Garo Armen, PhD

CPM Combinations

83

Combination Therapies Likely Key to Success

With CTLA-4 and PD-1 antagonists, different patients respond differently

– Differences in responses to each CPM or combo

– Differences in time course of response

– Reflects mutational burden, in part

Studies with proxy TAAs such as NY-ESO-1 demonstrate heterogeneity of immune education

– Implies that patients have different baseline degrees of Immune Education and different degrees and types of mechanisms of effector evasion

Redundancy of Inhibitory CPs suggests need for or benefit from patient-specific combination CPM use

Optimal therapy will tailor combination use of CPMs and potentially vaccines to match needs of individual

84

Cancer- In Limbo between Self & Non-Self

Mutational Heterogeneity in Cancer

Taking off brakes may be enough

May need agonists, Unclear how widely vaccines, adjuvants, etc.

Immuno-Rx will work

Lawrence MS et al. Nature 2013; 499: 214-18

100 mutations per Mbase = 0.01% of genome

85

Checkpoints and Vaccines Synergize

OX40 agonist and vaccine in mice Vaccine + CTLA-4 inhibitor (ipilimumab) better than either alone in prostate cancer

Jensen et al., 2010 Semin Oncol. 37(5):524-32.

Ipi monotherapy failed in Ph 3 (no stat. sign. vs. placebo)

Importantly: 20% of patients alive at 80 months on

PROSTVAC+ipi 10mg/Kg

Source: 2015 Genitourinary Cancers Symposium, abstract no. 172; Bavarian Nordic press release

86

HSPPC-96 + Anti-CTLA-4 Ab in Mouse SM1 Therapy

Set-up gp96 gp96 gp96 gp96 gp96 gp96

Day 0 3 4 6 7 9 10 12 15 18 Monitor

tumor growth

SM1 Tumor Ab Ab Ab Challenge (ID)

Results

SM1 (breast cancer)

Buffer Antibody gp96 Antibody + gp96

(mm) 25 25

0/7 (0%) 1/7 (14%) 1/6 (17%) 6/7 (86%)

20 20

15 15 diameter 10 10

5 5 tumor 0 0

. 0 7 12 16 21 25 28 32 36 0 7 12 16 21 25 28 32 36 0 7 12 16 21 25 28 32 36 0 7 12 16 21 25 28 32 36

Avg

Days post tumor challenge

Agenus data

87

Realizing New Optimized Combination Strategies

An armamentarium to tackle a range of human malignancies

Example: PD-1 and CTLA-4 combination Agenus’ diverse I-O portfolio

Partnered with INCY: GITR, OX40 agonist antibodies and TIM3, LAG3 antagonist antibodies

Postow M et al., NEJM 2015 SMIs

88

Translational Medicine in Immuno-Oncology

What is the initial pathobiology?

Has the patient seen the tumor as non-self?

What immuno-suppressive mechanisms are blunting recognition of tumor? What checkpoint processes will block tumor killing?

Those already in place and those induced by therapy

What choice of therapy is implied?

What combination of immuno-education strategies and CPMs should we try?

Have we achieved the desired pharmacological effects?

– Have our interventions produced their effects?

Will we achieve clinical benefit?

– Will the interventions lead to tumor control?

– Are we heading toward immune side effects?

– Should we alter the clinical intervention?

89

R&D Day

Introduction Garo Armen, PhD Immuno-Oncology Overview Bob Stein, MD, PhD Tumor Recognition John Castle, PhD Glioblastoma (GBM) Orin Bloch, MD—NW U Agenus / 4-Antibody Robert Burns, PhD Monoclonal Antibodies Marc van Dijk, PhD Checkpoint Modulators (CPMs) Nicholas Wilson, PhD Combination Immunotherapy Charles Drake, MD—JHU Science Wrap-up Bob Stein, MD, PhD

Discussion – Q&A All

Closing Remarks Garo Armen, PhD

R&D Day

Introduction Garo Armen, PhD Immuno-Oncology Overview Bob Stein, MD, PhD Tumor Recognition John Castle, PhD Glioblastoma (GBM) Orin Bloch, MD—NW U Agenus / 4-Antibody Robert Burns, PhD Monoclonal Antibodies Marc van Dijk, PhD Checkpoint Modulators (CPMs) Nicholas Wilson, PhD Combination Immunotherapy Charles Drake—MD JHU Science Wrap-up Bob Stein, MD, PhD Discussion – Q&A All

Closing Remarks Garo Armen, PhD

Three Synergistic Immune-Modulating Platform

Poised to Create Best-in-Class Immunotherapies

+ Ph 2 in ndGBM

+ Ph 2 w HerpV

Heat Shock Protein-Based Vaccines

QS-21

Checkpoint Stimulon® Modulators

+ Ph 3 Malaria Adjuvant (CPMs)

+ Ph 3 Shingles

92

Agenus R&D Analysts Day

May 14th. 2015

Driving the immune a system to fight cancer and infectious disease

EX-99.2

Exhibit 99.2

Agenus Announces Oral Presentation at ASCO Highlighting Improved Survival

with Prophage Immunotherapy in Brain Cancer Compared to Historical Controls

Improved median Overall Survival and Progression Free Survival observed for Prophage-treated patients with Lower PD-L1 expression on peripheral blood monocytes at baseline

LEXINGTON, MA – May 14, 2015 – Agenus Inc. (NASDAQ: AGEN), an immunology company developing innovative treatments for cancers and other diseases, today announced that data on continuing survival from a Phase 2 study of its Prophage vaccine in glioblastoma multiforme (GBM) has been selected for an oral presentation at the 2015 ASCO Annual Meeting, to be held May 29 – June 2, 2015 in Chicago. The presentation, abstract #2011 entitled “Newly diagnosed glioblastoma patients treated with an autologous heat shock protein peptide vaccine: PD-L1 expression and response to therapy,” will be presented during the Clinical Science Symposium at 8:48am CST by Orin Bloch, MD, Khatib Professor of Neurological Surgery and Assistant Professor of Neurological Surgery and Neurology at Northwestern University Feinberg School of Medicine.

Study Highlights

• Patients treated with Prophage added to Standard of Care (SOC) showed significantly longer progression free survival and overall survival compared to historical data for patients receiving SOC alone

• Patients in the study showed a degree of elevation of PD-L1 on their peripheral blood monocytes and in tumor infiltrating macrophages

• In patients who had less PD-L1 on monocytes at baseline, the median Overall Survival (mOS) was approximately 45 months, with a significant proportion of patients alive without progression for more than 3.5 years

• In patients who had more PD-L1 on monocytes at baseline, the mOS was 18 months, still better than expected from historical data

“These are impressive results in a disease that has few effective treatments or promising candidates in development,” commented Orin Bloch, M.D. “We’re particularly gratified to observe the very impressive survival data in the half of our patients with lower PD-L1 monocyte expression at baseline. Not only is the median Overall Survival much better than expected, but there is a significant proportion of patients who are living longer than expected without progression. We are also intrigued by the possibility that blocking the PD-1 / PD-L1 axis in conjunction with Prophage in patients with elevated PD-L1 may allow the outcomes observed in the lower PD-L1 group to extend to these patients as well.”

Study Details

The Phase 2 single-arm trial enrolled forty-six adult patients newly diagnosed with GBM from eight centers in the U.S. Each patient received standard treatment of surgical resection followed by chemoradiation. Within five weeks of completing radiotherapy, patients received weekly Prophage

injections for four weeks followed by monthly Prophage injections, and adjuvant temozolomide until the depletion of vaccine or tumor progression. Expression of PD-L1 has been shown to be elevated in patients with GBM, and each patient was also evaluated for PD-L1 expression as a predictor of survival.

The primary endpoint of the trial was overall survival. Median progression-free survival in the trial was 17.8 months (95% CI, 11.3 – 21.6), and median overall survival was 23.8 months (95% CI, 19.8 – 30.2). This compares to a historical overall survival of 14.8 – 18.8 months for patients receiving standard of care alone. The vaccine was well-tolerated in the study with no severe adverse events attributed to the treatment.

The median overall survival for patients with high PD-L1 expression (above the median, 54% of monocytes) was 18.0 months (95% CI, 10.0 – 23.3). Median overall survival for patients with low PD-L1 expression was 44.7 months (95% CI not calculable).

“These data continue to impress, and we’re gratified they were selected by ASCO for an oral presentation,” commented Dr. Robert Stein, Chief Scientific Officer of Agenus. “Prophage monotherapy, in patients with low PD-L1 expression in peripheral blood monocytes at baseline, appears to show a substantial increase in survival compared to historical controls. Registrational study planning is underway for Prophage, and we will provide further updates later this year.”

About Agenus

Agenus is an immunology company developing a series of Checkpoint Modulators for the treatment of patients with cancer, infectious diseases, and other immune disorders, heat shock protein (HSP)-based vaccines, and immune adjuvants. These programs are supported by three synergistic technology platforms. Agenus’ internal and partnered checkpoint modulator programs target GITR, OX40, CTLA-4, LAG-3, TIM-3, PD-1 and other undisclosed immune-modulatory targets. The company’s proprietary discovery engine Retrocyte Display^TM is used to generate fully human and humanized therapeutic antibody drug candidates. The Retrocyte Display platform uses a high-throughput approach incorporating IgG format human antibody libraries expressed in mammalian B-lineage cells. Agenus recently acquired a powerful yeast antibody display platform termed SECANT, developed by Celexion, LLC. SECANT allows rapid generation of soluble, full-length human antibodies. SECANT and Agenus’ mammalian antibody display platform have complementary strengths and further bolster Agenus’ abilities to generate and optimize fully human monoclonal antibodies. Agenus’ heat shock protein-based vaccines have completed Phase 2 studies in newly diagnosed glioblastoma multiforme, and in the treatment of herpes simplex viral infection; the heat shock protein-based vaccine platform can generate personalized as well as off the shelf products. The company’s QS-21 Stimulon^® adjuvant platform is extensively partnered with GlaxoSmithKline and with Janssen Sciences Ireland UC and includes several candidates in Phase 2 trials, as well as shingles and malaria vaccines which have successfully completed Phase 3 clinical trials. For more information, please visit www.agenusbio.com, or connect with the company on Facebook, LinkedIn, Twitter and Google+; information that may be important to investors will be routinely posted in these locations.

Forward-Looking Statement

This press release contains forward-looking statements that are made pursuant to the safe harbor provisions of the federal securities laws, including statements regarding the upcoming presentation at ASCO, the potential application of the Company’s product candidate in the remediation of GBM, and

2

potential future clinical trial plans. 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. Agenus cautions investors not to place considerable reliance on the forward-looking statements contained in this release. These statements speak only as of the date of this press release, 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.

Contacts:

Media

Brad Miles

BMC Communications

646-513-3125

bmiles@bmccommunications.com

Investors

Andrea Rabney/ Jamie Maarten

Argot Partners

212-600-1902

andrea@argotpartners.com

jamie@argotpartners.com

3