March 2017
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 most recent Annual Report on form 10-K or Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission 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
Broad I-O portfolio: enabling optimal combos 3
Agenus Five Year Growth Plan: balancing low & high risk initiatives Advance on most rapid path to BLA Develop, register, and launch anti-pd-1/ctla-4 mab combinations in validated indications Pursue novel breakthrough indications to expedite market entry Leverage novel targets for market expansion Pursue optimal I-O mab and vaccine combinations with anti-ctla-4 +/- anti-pd-1 Progress partnered programs (GITR, OX40, TIM-3, LAG-3) towards registration Advance Ab programs against innovative undisclosed targets to the clinic Engage in strategic partnerships 4
Current partnerships QS-21 Stimulon : adjuvant for Shingrix GSK filed for registration in U.S., Canada and Europe Royalties and milestones partly monetized 1 undisclosed target Lead selection completed Up to $100 million in milestones Pre-clinical: LAG-3, TIM-3, TIGIT, 2 undisclosed Royalty rates are generally 6-12%* Clinical: GITR, OX40 Royalty rate 15% Up to $510 million in milestones across all programs * *Incyte eligible for 15% royalty for TIGIT 5
Clinical Strategy
New clinical development paradigm compressed Risk AGEN1884 / AGEN2034 + Vaccine AGEN1884 / AGEN2034 Solid Tumors Efficacy unknown AGEN1884 / AGEN2034 + Novel CPM (A, B, C) AGEN1884 / AGEN2034 Solid Tumors Efficacy proven Conventional time to BLA AGEN1884 = anti-ctla-4 mab AGEN2034 = anti-pd-1 mab CPM = checkpoint modulator 10 years 7
anti-ctla-4 + anti-pd-1: first clinically validated I-O mab combo anti-ctla-4 (low dose) combined with anti-pd-1/pd-l1 is the only validated mab combination with improved efficacy and safety profile Near doubling of clinical response - from 25% to ~57% in NSCLC (1) Control of CTLA-4 + PD-1/PD-L1 targeted therapies could offer a pricing advantage Provides a foundation for mabs against novel checkpoints that are yet to show efficacy in the absence of CTLA-4 antagonism 1. Hellmann et al. Lancet Oncol 2017 *Anti-CTLA-4 antibody AGEN1884 is partnered with Recepta for certain South American territories 8
Targeting PD-1 has clinical benefit but combining with CTLA-4 antagonism works better anti-ctla-4 (low dose) combination with anti-pd-1/pd-l1 reduces development risk and expands markets anti-ctla-4 and anti-pd-1 mab combination is already approved in metastatic melanoma & almost doubles clinical benefit in 1L NSCLC (1) CTLA-4 + PD-1/PD-L1 antagonists +/- mabs targeting novel checkpoints have shown compelling data in preclinical models 1. Hellmann et al. Lancet Oncol 2017 *Anti-CTLA-4 antibody AGEN1884 is partnered with Recepta for certain South American territories 9
Metastatic virally induced malignancies*: appealing target for Agenus Clinical development: SOC marginally changed after the approval of Avastin in combination with chemo in 1L No effective treatment options in 2L; unmet medical need Clinical activity of other anti PD-X in virally induced and HPV driven malignancy (HNSCC HPV+) suggests that AGEN1884 administration could lead to an ORR 15% in all comers, > 20% in PD-L1+ Regulatory: US: Possibility of applying for Breakthrough Designation, assuming hypotheses are backed up by clinical data, Accelerated Approval possible EU: Possibility of applying for conditional marketing authorization Commercial: Potential niche opportunity with most of the patients from Japan and South Korea where premium prices for unmet medical needs are commonly given and where there is no off-label use reimbursed * Anticipated in cervical cancer 10
AGEN2034 (anti-pd-1) and AGEN1884 (anti-ctla-4): projected clinical inflection points 2017 2018 2019 2020 2021 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 First patient for 2034 dose escalation Phase 1 n = 30 Dose is established 2L Virally-induced Cancer ** First patient for dose escalation 2034 + 1884 Phase 1b n = 30 Virally-induced Cancer PD-1 vs PD-1 + CTLA-4 vs SOC * Top line data *** US filing US approval ** ** * Anticipated in cervical cancer ** Projections 11
Preclinical data
Sculpting the immune response to maximize clinical benefit Checkpoint mabs Anti-4-1BB Anti-OX40** Anti-GITR** Checkpoint mabs Anti-CTLA-4* Anti-PD-1* Anti-TIGIT Anti-TIM-3** Anti-LAG-3** Vaccine Platforms Prophage AutoSynVax (ASV ) PhosphoSynVax (PSV ) Neoantigen vaccines: ASV, PSV Adjuvant: QS-21 Stimulon Anti-CTLA-4* Anti-PD-1* * Partnered with Recepta for certain South American territories ** Partnered with Incyte 13
Integrated antibody discovery technologies, combined with immunology expertise 14
Agenus anti-ctla-4 mab improves primate vaccine response A n ti-h B s A g Ig G (U /m L ) S F U /1 x 1 0 6 P B M C Antibody Vaccine Anti-CTLA-4 antibody AGEN1884 + Hepatitis B surface antigen (HBsAg) vaccine Humoral Response Cellular Response 2,0 0 0,0 0 0 1,5 0 0,0 0 0 A G E N 1 8 8 4 (N = 6 ) C o n tr o l (N = 6 ) 5 0 0 4 0 0 A G E N 1 8 8 4 Is o ty p e c o n tro l 1,0 0 0,0 0 0 3 0 0 2 0 0 5 0 0,0 0 0 1 0 0 0-7 1 5 2 9 4 3 5 9 6 9 0-4 0 8 1 5 2 2 2 9 3 6 4 3 5 0 5 7 6 7 A d m in is tra tio n s o f a n tib o d y o r v e h ic le (c o n tr o l) p lu s H B s A g v a c c in e Internal data (unpublished) D a y s A fte r In itia l D o s in g 15
P D -L 1 o r P D - L 2 b in d in g ( % ) IL - 2 (p g /m l) AGEN2034: Anti-PD-1 antagonist antibody PD-1 inhibits TCR-induced signaling to impair T cell effector function Response rates observed with an PD-1 antagonist in a range of solid and hematological tumor settings AGEN2034 binds to PD-1 with high affinity (nm) and potently inhibits PD-1 binding to PD-L1/2 1 0 0 5 0 P D -L1 P D -L2 AG EN2034 iso type AG EN2034 iso type AGEN2034 enhances T cell responsiveness to suboptimal TCR activation 3 0 0 2 0 0 1 0 0 AG EN2034 Is o ty p e 0-5 -4-3 -2-1 0 1 2 A n tib o d y ( lo g g /m L ) 0-7 -6-5 -4-3 -2-1 0 1 2 A n tib o d y ( lo g g /m L ) Internal data (unpublished) 16
AGEN1884 combines in primary T cell assays with PD-1:PD-L1 blockade (as well as LAG-3) Isotype Pembrolizumab Internal data (unpublished) 17
Business
Projected milestones 2016 2017 2018 Accomplishments Clinical Deliverables Clinical Activity & Readouts Three CPM mabs in clinic CTLA-4 antagonist (AGEN1884)* GITR agonist (INCAGN1876)** OX40 agonist (INCAGN1949)** Clinical Development team with I-O development success on board QS-21 Stimulon containing Shingles vaccine filed for regulatory approval * Partnered with Recepta for certain South American rights ** Partnered with INCY Anticipated in cervical cancer Clinical trials Initiate Ph 1 for PD-1 antagonist (AGEN2034)* monotherapy Initiate virally-induced cancer trial (2L) Initiate Ph 1b with AGEN1884* with AGEN2034* Initiate Ph 1 with AutoSynVax Clinical results Optimal monotherapy dose for AGEN2034* Optimal combination dose of AGEN2034* + AGEN1884* Clinical responses Data from 30 patients Initial immune biomarker data from 6- patient Ph 1 ASV proof-of-mechanism trial Complete enrollment for 2 nd line virally-induced cancer cohort Top line data for the virallyinduced cancer cohort: Response rate Duration of response Safety and tolerability 19
Management Team Garo Armen, PhD, Chairman & CEO Elan Corporation, plc, Protagenic Therapeutics, Founder - Children of Armenia Fund (COAF) Robert Stein, MD, PhD, President, R&D Incyte Pharmaceuticals, Ligand Pharmaceuticals, Dupont/Merck, Roche, KineMed, Merck, Sharp & Dohme Jennifer Buell, PhD, VP R&D and External Affairs Harvard Clinical Research, Bristol-Myers Squibb Christian Cortis, PhD, VP Business Development Synta Pharmaceuticals, Advanced Technology Ventures, Columbia University Jean-Marie Cuillerot, MD, Chief Medical Officer EMD Serono, Bristol-Myers Squibb, University Louis Pasteur Alex Duncan, PhD, Chief Technology Officer Actigen, Affitech A/S, Astra Zeneca, Cambridge Antibody Technology Christine Klaskin, VP Finance Arthur Andersen, George Washington University Michelle Linn, VP Corporate Communications Linnden Communications, Ogilvy PR/Feinstein Kean, Chair of Women In Bio Boston Chapter Karen Valentine, JD, Chief Legal Officer & General Counsel Palmer and Dodge LLP 20