AGENUS INC

Competition in the pharmaceutical and biotechnology industries is intense. Many pharmaceutical or biotechnology companies have products on the market and are actively engaged in the research and development of products for the treatment of cancer.

Many competitors have substantially greater financial, manufacturing, marketing, sales, distribution, and technical resources, and more experience in research and development, clinical trials, and regulatory matters, than we do. Competing companies developing or acquiring rights to more efficacious therapeutic products for the same diseases we are targeting, or which offer significantly lower costs of treatment, could render our products noncompetitive or obsolete. See Part I-Item 1A. “Risk Factors-Risks Related to the Commercialization of Our Product Candidates-Our competitors may have superior products, manufacturing capability, selling and marketing expertise and/or financial and other resources.”

Academic institutions, governmental agencies, and other public and private research institutions conduct significant amounts of research in biotechnology, medicinal chemistry and pharmacology. These entities have become increasingly active in seeking patent protection and licensing revenues for their research results. They also compete with us in recruiting and retaining skilled scientific talent.

The I-O drug landscape is crowded with several competitors developing assets against a number of targets. Our development plans are spread across various indications and lines of therapy, either alone or in combination with other assets. Our competitors range from small cap to large cap companies, with assets in pre-clinical or clinical stages of development. Therefore, the landscape is dynamic and constantly evolving. We and our partners have I-O antibody programs currently in clinical stage development targeting various pathways including PD-1, CTLA-4, TIM-3, LAG-3, CD73, TGFb, CD137, ILT2, and TIGIT. We are aware of many companies that have antibody-based products on the market or in clinical development that are directed to the same biological targets as these programs, including, without limitation, the following: (1) BMS markets ipilimumab, an anti-CTLA-4 antibody, nivolumab, an anti-PD-1 antibody, and relatlimab, an anti-LAG-3 antibody, and is currently developing agents targeting TIGIT, TIM-3, CD137 and TGFb, (2) Merck has an approved anti-PD-1 antibody, pembrolizumab, and has an anti-CTLA-4, anti-TIGIT and LAG-3 antagonists recruiting in clinical trials, (3) Regeneron has an approved anti-PD-1 antibody, cemiplimab, and an antibody targeting LAG-3 in the clinic, (4) Roche/Genentech has an approved anti-PD-L1 antibody, atezolizumab, a late-stage anti-TIGIT antibody, an anti-TGFb antibody as well as bispecific antibodies targeting CD137 and LAG-3 in clinical development, (5) AstraZeneca has an approved anti PD-L1 antibody, durvalumab, an approved anti-CTLA-4 antibody, tremelimumab, and has monoclonal antibodies targeting CD73, as well as bispecific antibodies targeting CTLA-4, TIGIT, TIM-3 in clinical development, (6) Merck KGaA has an approved anti-PD-L1 antibody, avelumab, as well as clinical assets including an anti-TIGIT antibody and bispecific antibodies targeting LAG-3 and TGFβ, (7) GSK has an approved anti PD-1 antibody, dostarlimab, as well as antibodies targeting TIM-3, LAG-3 and TIGIT in the clinic (8) Coherus Biosciences has an approved anti-PD-1 antibody, toripalimab, (9) Incyte has an approved anti-PD-1 antibody, retifanlimab, and clinical assets targeting LAG-3 and CD73, (10) Beigene Ltd has an approved anti-PD1 antibody, tislelizumab, and has clinical assets targeting LAG-3 and TIGIT, (11) Checkpoint Therapeutics has an approved anti-PD-L1 antibody, cosibelimab. Besides these PD-1 and PD-L1 antibodies that are approved in the U.S., we are also aware of competitors with approved PD-1 and PD-L1 agents in ex-U.S. geographies such as China. These include Akeso Biopharma, CStone Pharmaceuticals, Harbin

Gloria Pharmaceuticals (Arcus Bioscience has rights in North America, Europe, Japan and certain other territories), Harbor Biomed, Innovent Biologics, Jiangsu Alphamab/3D Medicines, Jiangsu HengRui Pharmaceuticals, Lee’s Pharmaceuticals, Lepu Biopharma (previously Taizhou Houdeaoke Technology), Qilu Pharmaceutical Co Ltd, Shanghai Henlius Biotech Co Ltd, Shanghai Junshi Biosciences (Coherus BioSciences has rights to co-develop in U.S. and Canada), Shanghai Pharmaceuticals, Shenzhou Cell Engineering, Sichuan Kelun Botail Biomedicine and Sino Biopharmaceuticals.

In addition to the companies noted above, we are also aware of additional competitors with clinical-stage PD-1/PD-L1 agents, both as monospecific and bispecific antibodies, including but not limited to AbbVie, Amgen, Arcus Biosciences/Gilead, Biocad Ltd., Boehringer Ingelheim, Eli Lilly, Janssen Pharmaceuticals, Novartis, Ono, Pfizer, and Sanofi. In addition, we are also aware of pre-clinical monospecific or bispecific antibodies targeting PD-1 or PD-L1.

We are aware of companies developing “next-generation” anti-CTLA-4 assets, which may be competitive to our next-generation AGEN1181. These next-generation monospecific antibodies targeting CTLA-4 include but are not limited to Adagene, BioAtla, Harbour BioMed, OncoC4/BioNTech and Xilio Therapeutics. We are also aware of companies advancing preclinical or clinical stage CTLA-4 targeting bispecific antibodies or oncolytic viruses as a next-generation approach including but not limited to Biocad, Jiangsu Alphamab, Macrogenics, Replimune, Sichuan Baili Pharmaceuticals and Xencor.

There are additional competitors with clinical stage drug candidates against LAG-3, TIM-3, CD73, TGFb, CD137, and TIGIT. Some of these competitors include but are not limited to AbbVie, Arcus Biosciences/Gilead, Alligator Biosciences, Anaptsys Bio, Astellas, Beigene, Bicara Therapeutics, Boehringer Ingelheim, Compass Therapeutics, Compugen, Galapagos NV, Genmab, Innovent Biologics, iTeos Therapeutics, Jacobio Pharmaceuticals, Lokon Pharma, Lyvgen Biopharma, Macrogenics, Mereo Biopharma, Novartis, Oncotellic Therapeutics, Palvella Therapeutics, Pfizer, Replimune, Sanofi, Scholar Rock, Servier, Sirnaomics and Spine Therapeutics. There is no guarantee that our antibody product candidates will be able to successfully compete with our competitors’ antibody products and product candidates.

There are many therapies that are approved to treat colorectal cancer. This includes but is not limited to chemotherapy agents such as fluorouracil injection (“5FU”), irinotecan hydrochloride, leucovorin, oxaliplatin, capecitabine and trifluridine/tipiracil hydrochloride; infused anti-VEGF agents such as bevacizumab, ramucirumab, and ziv-aflibercept; immuno-oncology agents such as nivolumab, pembrolizumab and ipilimumab; anti-EGFR agents such as cetuximab and panitumumab; KRAS G12C inhibitors such as adagrasib and sotorasib; tucatinib, a HER2 antagonist; fruquintinib, an oral VEGFR antagonist; regorafenib, a tyrosine kinase inhibitor; and encorafenib, a BRAF V600E inhibitor.

There is significant competition to develop therapies to treat patients with refractory colorectal cancer (“CRC”). Companies that have clinical stage agents to treat refractory CRC include but are not limited to Abbvie, which is evaluating a c-Met inhibitor as a monotherapy; Adagene, which is evaluating a CTLA-4 inhibitor in combination with pembrolizumab; Exelixis, which is evaluating a tyrosine kinase inhibitor in combination with atezolizumab; Jiangsu Alphamab, which is evaluating a PD-L1xCTLA-4 bispecific antibody in combination with regorafenib; Merck, which is evaluating a CD47 inhibitor in combination with cetuximab and pembrolizumab; Replimune, which is evaluating its oncoloytic virus candidates in combination with bevacizumab and atezolizumab; Xilio Therapeutics, which is evaluating its CTLA-4 inhibitor in combination with atezolizumab.

Additionally, AGEN1571, our ILT2 antibody is now in clinical development. We are aware of other clinical stage anti-ILT2, both monospecific and bispecific antibodies, and anti-HLA-G antibodies that could compete with this program. These include but are not limited to, Bond Biologics/Sanofi, ImmuneOs Therapeutics, Invectys, Janssen, LG Chem, NGM Biopharmaceuticals, Pfizer and Tizona Therapeutics. We are also aware of competitor programs that are in preclinical development against this target. There is no guarantee that our antibody product candidates will be able to successfully compete with our competitors’ antibody products and product candidates.

In addition, and prior to regulatory approval, if ever, our other product candidates may compete for access to patients with other products in clinical development, with products approved for use in the indications we are studying, or with off-label use of products in the indications we are studying. We anticipate that we will face increased competition in the future as new companies enter markets we seek to address and scientific developments surrounding immunotherapy and other traditional cancer therapies continue to accelerate.

SaponiQx is developing QS-21 STIMULON. Several other vaccine adjuvants are in development or in use and could compete with QS-21 STIMULON for inclusion in vaccines. These adjuvants may include but are not limited to: (1) oligonucleotides, under development by Dynavax, (2) MF59, under development by Novartis, (3) IC31, under development by Intercell (now part of Valneva), (4) MPL, under development by GSK, (5) Matrix-MTM, under development by Novavax, (6) AS03 and additional AS portfolio members, under development by GSK, and (7) TQL 1055, under development by Adjuvance Technologies. In the past, we have provided QS-21 STIMULON to other entities under materials transfer arrangements. There is a risk that material provided pursuant to an MTA is used without our permission to develop synthetic formulations and/or derivatives of QS-21. In addition, other companies and academic institutions are developing saponin adjuvants, including derivatives and synthetic formulations. These sources may be competitive to our ability to execute future partnering and licensing arrangements involving QS-21 STIMULON. We are also aware of other manufacturers of QS-21. The existence of products developed by these and other competitors, or other products of which we are not aware, or which other companies may develop in the future, may adversely affect the marketability of products developed or sold using QS-21 STIMULON.

Even if we obtain regulatory approval to market our product candidates, the availability and price of our competitors’ products could limit the demand and the price we are able to charge for our product candidates. We may not be able to implement our business plan if the acceptance of our product candidates is inhibited by price competition or the reluctance of physicians to switch from existing methods of treatment to our product candidates, or if physicians switch to other new drug or biologic products or choose to reserve our product candidates for use in limited circumstances.