AGENUS INC

Competition in the pharmaceutical and biotechnology industries is intense. Many companies, including large pharmaceutical companies and specialized biotechnology companies, have products on the market or in development for the treatment of cancer. Many of these companies have substantially greater financial, manufacturing, development, commercial and regulatory resources 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 substantial research in biotechnology, medicinal chemistry, and pharmacology. These entities have increasingly sought patent protection and licensing revenues for their research results and also compete with us in recruiting and retaining skilled scientific talent.

The immuno-oncology drug landscape is highly competitive, with numerous companies developing assets against a wide range of targets. Our development programs span multiple indications and lines of therapy, both as monotherapies and in combination with other assets. Competitors range from small-cap to large-cap companies and include programs in both pre-clinical and clinical stages of development. As a result, the competitive landscape is dynamic and continually evolving. We and our partners currently have I-O antibody programs in clinical-stage development targeting several pathways, including PD-1, CTLA-4, TIM-3, LAG-3, CD73, TGFβ, CD137, ILT2, and TIGIT. We are aware of many companies with antibody-based products either approved or in clinical development that target these same biological pathways, including the following:

Bristol Myers Squibb markets Ipilimumab (anti-CTLA-4), Nivolumab (anti-PD-1), and Relatlimab (anti-LAG-3), and is developing agents targeting TIGIT, TIM-3, CD137, and TGFβ.

Merck & Co. markets Pembrolizumab (anti-PD-1) and has anti-CTLA-4, anti-TIGIT, and LAG-3 antagonists recruiting in clinical trials.

Regeneron Pharmaceuticals markets Cemiplimab (anti-PD-1) and has an antibody targeting LAG-3 in clinical development.

Roche / Genentech market Atezolizumab (anti-PD-L1), have a late-stage anti-TIGIT antibody, an anti-TGFβ antibody, and bispecific antibodies targeting CD137 and LAG-3 in clinical development.

AstraZeneca markets Durvalumab (anti-PD-L1) and Tremelimumab (anti-CTLA-4), and has monoclonal antibodies targeting CD73 as well as bispecific antibodies targeting CTLA-4, TIGIT, and TIM-3 in clinical development.

Merck KGaA markets Avelumab (anti-PD-L1) and has clinical assets including an anti-TIGIT antibody and bispecific antibodies targeting LAG-3 and TGFβ.

GSK markets Dostarlimab (anti-PD-1) and has antibodies targeting TIM-3, LAG-3, and TIGIT in clinical development.

Coherus BioSciences markets Toripalimab (anti-PD-1).

Incyte markets Retifanlimab (anti-PD-1) and has clinical assets targeting LAG-3 and CD73.

BeiGene markets Tislelizumab (anti-PD-1) and has clinical assets targeting LAG-3 and TIGIT.

Checkpoint Therapeutics markets Cosibelimab (anti-PD-L1).

In addition to PD-1 and PD-L1 antibodies approved in the United States, several competitors have approved PD-1 or PD-L1 agents in markets outside the United States, including China. These companies include Akeso Biopharma, CStone Pharmaceuticals, Harbin Gloria Pharmaceuticals (with Arcus Biosciences holding rights in North America, Europe, Japan, and certain other territories), Harbour BioMed, Innovent Biologics, Jiangsu Alphamab Biopharmaceuticals / 3D Medicines, Jiangsu Hengrui Pharmaceuticals, Lee’s Pharmaceutical Holdings, Lepu Biopharma (formerly Taizhou Houdeaoke Technology), Qilu Pharmaceutical, Shanghai Henlius Biotech, Shanghai Junshi Biosciences (with Coherus BioSciences holding co-development rights in the U.S. and Canada), Shanghai Pharmaceuticals, Shenzhou Cell Engineering, Sichuan Kelun Botai Biomedicine, and Sino Biopharmaceutical.

In addition to the companies noted above, we are aware of additional competitors developing clinical-stage PD-1/PD-L1 agents, including both monospecific and bispecific antibodies. These companies include, but are not limited to, AbbVie, Amgen, Arcus Biosciences / Gilead Sciences, Biocad Ltd., Boehringer Ingelheim, Eli Lilly and Company, Janssen Pharmaceuticals, Novartis, Ono Pharmaceutical, Pfizer, and Sanofi. 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 that may compete with our next-generation botensilimab. 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 next-generation approaches, including but not limited to Biocad Ltd., Jiangsu Alphamab Biopharmaceuticals, MacroGenics, Replimune, Sichuan Baili Pharmaceutical, and Xencor.

There are additional competitors with clinical-stage drug candidates targeting LAG-3, TIM-3, CD73, TGFβ, CD137, and TIGIT. These competitors include, but are not limited to, AbbVie, Arcus Biosciences / Gilead Sciences, Alligator Bioscience, AnaptysBio, Astellas Pharma, 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, Oncotelic Therapeutics, Palvella Therapeutics, Pfizer, Replimune, Sanofi, Scholar Rock, Servier, Sirnaomics, and Spine Therapeutics. There is no guarantee that our antibody product candidates will successfully compete with our competitors’ antibody products and product candidates.

There are many therapies approved to treat colorectal cancer, including but not limited to chemotherapy agents such as Fluorouracil (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 for patients with refractory colorectal cancer (“CRC”). Companies with clinical-stage agents targeting refractory CRC include, but are not limited to, AbbVie, which is evaluating a c-Met inhibitor as 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 Biopharmaceuticals, which is evaluating a

PD-L1×CTLA-4 bispecific antibody in combination with Regorafenib; Merck & Co., which is evaluating a CD47 inhibitor in combination with Cetuximab and Pembrolizumab; Replimune, which is evaluating oncolytic virus candidates in combination with Bevacizumab and Atezolizumab; and Xilio Therapeutics, which is evaluating a CTLA-4 inhibitor in combination with Atezolizumab.

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

Prior to regulatory approval, if obtained, our other product candidates may compete for patient access with other clinical-stage products, with products already approved for the indications we are studying, or with off-label use of products in those indications. We expect competition to increase as new companies enter these markets and scientific developments in immunotherapy and other cancer treatments continue to accelerate.

SaponiQx is developing QS-21 STIMULON. Several other vaccine adjuvants are either in development or currently in use and could compete with QS-21 STIMULON for inclusion in vaccines. These adjuvants include, but are not limited to: (1) oligonucleotides developed by Dynavax Technologies; (2) MF59 developed by Novartis; (3) IC31 developed by Intercell (now part of Valneva); (4) MPL developed by GSK; (5) Matrix-M™ developed by Novavax; (6) AS03 and other AS portfolio adjuvants developed by GSK; and (7) TQL-1055 developed by Adjuvance Technologies.

Historically, we have supplied QS-21 STIMULON to other entities under materials transfer agreements (“MTAs”). There is a risk that materials provided under an MTA could be used without our permission to develop synthetic formulations or derivatives of QS-21. In addition, other companies and academic institutions are developing saponin adjuvants, including derivatives and synthetic formulations, which may compete with 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, as well as products of which we may not currently be aware or that may be developed in the future, could 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 pricing of competing products may limit demand and the price we can charge. We may not be able to execute our business plan if adoption of our product candidates is limited by price competition, physician reluctance to switch from existing treatments, or physician preference for other new drug or biologic therapies or for reserving our product candidates for limited use.