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Agenus R&D Day May 14th 2015
immune a system to fight cancer and infectious disease
Note Regarding Forward-Looking Statements
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
Introduction Garo Armen, PhD
Overview Bob Stein, MD, PhD
Tumor Recognition John Castle, PhD
Glioblastoma (GBM) Orin Bloch, MD NW U
Agenus / 4-Antibody Robert Burns, PhD
Antibodies Marc van Dijk, PhD
Checkpoint Modulators (CPMs) Nicholas Wilson, PhD
Combination Immunotherapy Charles Drake, MD JHU
Science Wrap-up Bob Stein, MD, PhD
Three Synergistic Immune-Modulating Platform
Poised to Create Best-in-Class Immunotherapies
Heat Shock Protein-Based Vaccines
QS-21 Checkpoint Stimulon Modulators
Malaria Adjuvant (CPMs)
Merck/Agenus CPM Collaboration: Focus on Oncology
Established April 2014
Uses Agenus monoclonal antibody platform
Two undisclosed targets
Financial considerations
Up to $100 MM milestones per successful compound Mid-single digit royalties
Incyte/Agenus Immuno-Oncology Collaboration
Established February 2015 Initial focus on 4 CPM targets:
GITR and OX40 agonists
TIM-3 and LAG-3 antagonists
$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)
Partnered Not Partnered
QS-21 Stimulon Saponin Adjuvant
strong antibody and cell-mediated immune responses Safe & well tolerated in >50,000 people
Robust Phase 3 Results with Shingles Vaccine
Efficacy: 97% 50-70%
Target population: 370M
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
Closing Remarks Garo Armen, PhD
The Immune System defends from enemies from without
The Immune System defends from enemies from without & within
Immunological Surveillance
(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.
Accumulated Mutations Drive Cancers
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+)
Cancer- In Limbo between Self & Non-Self
Mutational Heterogeneity in Cancer
Taking off brakes may be enough
agonists, Unclear how widely vaccines, adjuvants, etc.
Lawrence MS et al. Nature 2013; 499: 214-18
100 mutations per Mbase = 0.01% of genome
Heat-Shock-Protein (HSP)-based
A strategy for Tumor-Specific Immuno-education
Pre-Clinical Overview
The Immune System Can Defeat Cancer
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
Na ve mouse Mouse forms Mouse Cured tumor mass Of Tumor A
Requires immune system tumor A NOT
Requires T Cells & NK Cells to tumor B
Adapted from Srivastava 2002 Ann Rev
Immunity is Individually Tumor Specific
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 + -
Basombrio 1970 Cancer Res. 30:2458
Heat Shock Protein Fractions Confer Immunity
hsp70 hsp90 hsp110 gp96 grp170
Tumor cell Proteins liberated Proteins tested
in Heat Shock Proteins (HSP) from tumor cell tumor rejection assays elicit anti-cancer immunity
Tumor DAY 0 7 14 size
MONITOR TUMOR GROWTH Days post tumor
Heat Shock Proteins (HSPs)
the Intracellular Proteome
Cellular Peptides Chaperoning by HSPs
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
Prophage Mechanism of Action
Heat-Shock-Protein (HSP)-based Vaccines
Personalized Immuno-education
Prophage confers tumor-specific immunity
Heat Shock Protein bound tumor antigens
Intradermal injection
Prophage: Sporadic Efficacy in Previous Studies
Patient remains disease-free at 10+ years