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What changed in AGENUS INC's 10-K — 2024 vs 2025

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Paragraph-level year-over-year comparison of AGENUS INC's 2024 and 2025 10-K annual filings, covering the Business, Risk Factors, Legal Proceedings, Cybersecurity, MD&A and Market Risk sections. Every new, removed and edited paragraph is highlighted side-by-side so you can see exactly what management changed in the 2025 report.

+422 added−471 removedSource: 10-K (2026-03-16) vs 10-K (2025-03-17)

Top changes in AGENUS INC's 2025 10-K

422 paragraphs added · 471 removed · 317 edited across 8 sections

Item 1. Business

Business — how the company describes what it does

90 edited+48 added−80 removed17 unchanged
Biggest changeWe 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.
Biggest changeRoche / 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. 5. 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. 6.
The FDA may also require confirmatory trials, post-marketing testing, and extra surveillance to monitor the effects of approved products, or place conditions on any approvals that could restrict the commercial applications of these products. Once approved, the labeling, advertising, promotion, marketing, and distribution of a drug or biologic product must be in compliance with FDA regulatory requirements.
The FDA may also require confirmatory trials, post-marketing testing, and extra surveillance to monitor the effects of approved products, or place conditions on any approvals that could restrict the commercial 9 applications of these products. Once approved, the labeling, advertising, promotion, marketing, and distribution of a drug or biologic product must be in compliance with FDA regulatory requirements.
The SEC maintains an Internet site that contains reports, proxy and information statements, and other information regarding issuers that file electronically with the SEC at www.sec.gov. The contents of the websites referred to above are not incorporated into this filing. Further, our references to the URLs for these websites are intended to be inactive textual references only.
The SEC maintains an Internet site that contains reports, proxy and information statements, and other information regarding issuers that file electronically with the SEC at www.sec.gov. 12 The contents of the websites referred to above are not incorporated into this filing. Further, our references to the URLs for these websites are intended to be inactive textual references only.
The license agreements also contain customary representations and warranties, mutual indemnification, confidentiality and arbitration provisions. Regulatory Compliance Governmental authorities in the United States and other countries extensively regulate the pre-clinical and clinical testing, manufacturing, labeling, storage, record keeping, advertising, promotion, export, marketing and distribution, among other things, of our investigational product candidates.
The agreements also include customary representations and warranties, mutual indemnification, confidentiality, and arbitration provisions. Regulatory Compliance Governmental authorities in the United States and other countries extensively regulate the pre-clinical and clinical testing, manufacturing, labeling, storage, record keeping, advertising, promotion, export, marketing and distribution, among other things, of our investigational product candidates.
“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.
“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.
The total amounts payable to Ligand are subject to a 50% reduction in the event total payments to Ligand exceed a specified return hurdle. The synthetic royalty is subject to a reduction if annual worldwide net sales exceed a specified level, and a cap on annual worldwide net sales if annual worldwide net sales exceed a higher specified level.
The total amounts payable to Ligand are subject to a 50% reduction if total payments to Ligand exceed a specified return hurdle. The synthetic royalty is also subject to reduction if annual worldwide net sales exceed a specified level and is subject to a cap on annual worldwide net sales if sales exceed a higher specified level.
In February 2017, we and Incyte amended the terms of the original collaboration agreement to, among other things, convert the GITR and OX40 programs from profit-share to royalty-bearing programs with royalties on global net sales at a flat 15% rate for each.
In February 2017, we and Incyte amended the collaboration agreement to, among other things, convert the GITR and OX40 programs from profit-share to royalty-bearing programs, each with royalties on global net sales at a flat 15% rate.
On January 25, 2016, we entered into a second license agreement with Ludwig, on substantially similar terms, to develop CTLA-4 and PD-1 antibodies. Pursuant to the December 2014 license agreement, we made an upfront payment of $1.0 million to Ludwig.
On January 25, 2016, we entered into a second license agreement with Ludwig, on substantially similar terms, to develop our first generation CTLA-4 (zalifrelimab) and PD-1 antibodies. Pursuant to the December 2014 license agreement, we made an upfront payment of $1.0 million to Ludwig.
For each royalty-bearing product, we were eligible to receive (i) up to $155.0 million in future contingent development, regulatory, and commercialization milestones and (ii) tiered royalties on global net sales at rates generally ranging from 6%-12%.
For each profit-share product, we were eligible to receive up to $20.0 million in future contingent development milestones. For each royalty-bearing product, we were eligible to receive (i) up to $155.0 million in future contingent development, regulatory, and commercialization milestones and (ii) tiered royalties on global net sales generally ranging from 6% to 12%.
There is significant competition to develop therapies to treat patients with refractory colorectal cancer (“CRC”).
There is significant competition to develop therapies for patients with refractory colorectal cancer (“CRC”).
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.
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.
The license agreements may each be terminated as follows: (i) by either party if the other party commits a material, uncured breach; (ii) by either party if the other party initiates bankruptcy, liquidation or similar proceedings; or (iii) by us for convenience upon 90 days’ prior written notice.
Each license agreement may be terminated: (i) by either party if the other party commits a material breach that remains uncured; (ii) by either party if the other party initiates bankruptcy, liquidation, or similar proceedings; or (iii) by us for convenience upon 90 days’ prior written notice.
The scope of the FCPA includes interactions with certain healthcare professionals in many countries. Other countries have enacted similar anti-corruption laws and/or regulations. Competition 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.
The scope of the FCPA includes interactions with certain healthcare professionals in many countries. Other countries have enacted similar anti-corruption laws and/or regulations. Competition 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.
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.
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.
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 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.
In addition, the profit-share programs relating to two undisclosed targets were removed from the collaboration, with one reverting to Incyte and one to Agenus (the latter being our Fc enhanced TIGIT program), each with royalties on global net sales at a flat 15% rate.
In addition, the two undisclosed profit-share programs were removed from the collaboration, with one reverting to Incyte and the other reverting to us (our Fc-enhanced TIGIT program), each with royalties on global net sales at a flat 15% rate.
Basic Product Patent Expiration Year (Earliest Estimated Year) Botensilimab 2037 2037 Balstilimab 2037 2036 Zalifrelimab 2037 2036 AGEN2373 2038 2038 AGEN1777 2042 2042 INCAGN2390 2037 2037 INCAGN2385 2037 2037 INCAGN1876 2035 2035 9 AGEN1949 2037 To be determined AGEN1423 2041 To be determined AGEN1571 2043 2043 Various patents and patent applications have been exclusively licensed to us by the following entity: Ludwig Institute for Cancer Research On December 5, 2014, we entered into a license agreement with the Ludwig Institute for Cancer Research Ltd., or Ludwig, which replaced and superseded a prior agreement entered into between the parties in May 2011.
Basic Product Patent Expiration Year (Earliest Estimated Year) 8 Botensilimab 2037 2037 Balstilimab 2037 2036 Zalifrelimab 2037 2036 AGEN2373 2038 2038 AGEN1777 2042 2042 INCAGN2390 2037 2037 INCAGN2385 2037 2037 INCAGN1876 2035 2035 AGEN1949 2037 To be determined AGEN1423 2041 To be determined AGEN1571 2043 2043 Various patents and patent applications have been exclusively licensed to us by the following entity: Ludwig Institute for Cancer Research On December 5, 2014, we entered into a license agreement with the Ludwig Institute for Cancer Research Ltd.
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.
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.
In particular, we own patents and patent applications relating to our Retrocyte Display technology platform, a high throughput antibody expression platform for the identification of fully-human and humanized monoclonal antibodies. In addition, as we advance our research and development efforts with our institutional and corporate collaborators, we are seeking patent protection for certain newly identified therapeutic antibodies and product candidates.
In particular, we own patents and patent applications relating to our Retrocyte Display technology platform, a high-throughput antibody expression platform for the identification of fully human and humanized monoclonal antibodies. As we advance our research and development activities with institutional and corporate collaborators, we continue to seek patent protection for newly identified antibodies and product candidates.
Data from the NEST study demonstrated promising results with no clinical recurrences observed after a median follow-up of 18 months and 9 months for the NEST-1 arm and NEST-2 arm, respectively. The pMR rate improved to 47% in MSS tumors when median time to surgery was extended, indicating a potential benefit of an extended pre-operative window.
Data from the NEST study demonstrated promising results, with no clinical recurrences observed after a median follow-up of 18 months for the NEST-1 arm and 9 months for the NEST-2 arm. The pathological complete response (“pCR”) rate improved to 47% in MSS tumors when the median time to surgery was extended, suggesting a potential benefit from a longer pre-operative window.
XOMA On September 20, 2018, we, through our wholly-owned subsidiary, Agenus Royalty Fund, LLC, entered into a Royalty Purchase Agreement (the “XOMA Royalty Purchase Agreement”) with XOMA (US) LLC (“XOMA US”).
XOMA 6 On September 20, 2018, through our wholly owned subsidiary Agenus Royalty Fund, LLC, we entered into a Royalty Purchase Agreement with XOMA (US) LLC.
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.
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.
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 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.
In September 2015, we monetized a portion of the royalties associated with the GSK License Agreement to an investor group led by Oberland Capital Management for up to $115.0 million in the form of a non-dilutive royalty transaction.
In September 2015, we monetized a portion of the GSK royalty stream through a non-dilutive transaction with an investor group led by Oberland Capital Management for up to $115.0 million.
The December 2014 license agreement also obligates us to make potential milestone payments of up to $20.0 million for events prior to regulatory approval of licensed GITR, OX40 and TIM-3 products, and potential milestone payments in excess of $80.0 million if such licensed products are approved in multiple jurisdictions, in more than one indication, and certain sales milestones are achieved.
The agreement also requires us to make potential milestone payments of up to $20.0 million for events occurring prior to regulatory approval of licensed GITR, OX40, and TIM-3 products, and potential milestone payments in excess of $80.0 million if those licensed products are approved in multiple jurisdictions, approved for more than one indication, and achieve certain sales milestones.
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.
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 11 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.
Under each of these license agreements, we will also be obligated to pay low to mid-single digit royalties on all net sales of licensed products during the royalty period, and to pay Ludwig a percentage of any sublicensing income, ranging from a low to mid-double digit percentage depending on various factors.
Under both license agreements, we are also obligated to pay Ludwig low- to mid-single-digit royalties on all net sales of licensed products during the royalty period. In addition, we must pay Ludwig a percentage of any sublicensing income, ranging from a low- to mid-double-digit percentage depending on various factors.
After taking into account our obligations under the Ligand Purchase Agreement, XOMA Royalty Purchase Agreement and the recent status of our collaboration agreements, we remain eligible to receive up to approximately $136.3 million and $49.4 million and in potential development, regulatory, and commercial milestones from UroGen and Merck, respectively.
After taking into account our obligations under the Ligand Purchase Agreement, the XOMA Royalty Purchase Agreement, and the current status of our collaboration agreements, we remain eligible to receive up to approximately $49.4 million in potential development, regulatory, and commercial milestone payments from Merck & Co..
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 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.
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.
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.
Through various acquisitions, we own, co-own, or have exclusive rights to a number of patents and patent applications directed to various methods and compositions, including methods for identifying therapeutic antibodies and product candidates arising out of such entities’ technology platforms.
Through various acquisitions and collaborations, we own, co-own or have exclusive rights to patents and patent applications directed to methods and compositions, including methods for identifying therapeutic antibodies and product candidates arising from our technology platforms.
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.
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.
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.
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.
In October 2021, we announced that the first patient was dosed in the AGEN1777 Phase 1 clinical trial, triggering the achievement of a $20.0 million milestone and in December 2023, we announced that the first patient was dosed in an AGEN1777 Phase 2 clinical trial, triggering the achievement of a $25.0 million milestone.
In October 2021, the first patient was dosed in the Phase 1 trial, triggering a $20.0 million milestone, and in December 2023 the first patient was dosed in a Phase 2 trial, triggering a $25.0 million milestone.
We are also subject to cGMP, GCP, and GLP compliance obligations and are subject to inspection by international regulatory authorities. 10 International requirements may in some circumstances be more rigorous than U.S. requirements and may require additional investment in manufacturing process development, non-clinical studies, clinical studies, and record-keeping that are not required for U.S. regulatory compliance or approval.
International requirements may in some circumstances be more rigorous than U.S. requirements and may require additional investment in manufacturing process development, non-clinical studies, clinical studies, and record-keeping that are not required for U.S. regulatory compliance or approval.
These include Akeso Biopharma, CStone Pharmaceuticals, Harbin 11 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.
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.
Whether or not we have obtained FDA approval, we must generally obtain approval of a product by comparable regulatory authorities of international jurisdictions prior to the commencement of marketing the product in those jurisdictions.
Whether or not we have obtained FDA approval, we must generally obtain approval of a product by comparable regulatory authorities of international jurisdictions prior to the commencement of marketing the product in those jurisdictions. We are also subject to cGMP, GCP, and GLP compliance obligations and are subject to inspection by international regulatory authorities.
(“Gilead”), Incyte and Betta Pharmaceuticals Co., Ltd. (“Betta”)). Partnered Programs Bristol Myers Squibb In May 2021, we entered into a License, Development and Commercialization Agreement with BMS (the “BMS License Agreement”) pursuant to which we granted BMS an exclusive license to develop, manufacture and commercialize our proprietary TIGIT bispecific antibody program AGEN1777.
Partnered Programs Bristol Myers Squibb In May 2021, we entered into a License, Development and Commercialization Agreement with Bristol Myers Squibb ("BMS") under which we granted BMS an exclusive license to develop, manufacture and commercialize our TIGIT bispecific antibody program, AGEN1777.
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.
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.
The remaining three royalty-bearing programs in the collaboration targeting TIM-3, LAG-3 and one undisclosed target remain unchanged, and there are no more profit-share programs under the collaboration. Pursuant to the amended agreement, we received accelerated milestone payments of $20.0 million from Incyte related to the clinical development of INCAGN1876 (“GITR agonist”) and INCAGN1949 (“OX40 agonist”).
The remaining three royalty-bearing programs targeting TIM-3, LAG-3, and one undisclosed target remained unchanged, and the collaboration no longer included any profit-share programs. Pursuant to the amended agreement, we received accelerated milestone payments of $20.0 million from Incyte related to the clinical development of INCAGN1876 (GITR agonist) and INCAGN1949 (OX40 agonist).
The collaboration was initially focused on four immunotherapy programs targeting GITR, OX40, TIM-3 and LAG-3, and in November 2015, we expanded the alliance by adding three novel undisclosed immunotherapy targets. Pursuant to the terms of the original agreement, Incyte paid us $25.0 million in upfront cash.
The collaboration initially focused on four immunotherapy programs targeting GITR, OX40, TIM-3, and LAG-3. In November 2015, the alliance was expanded to include three additional undisclosed immunotherapy targets. Pursuant to the terms of the original agreement, Incyte paid us $25.0 million in upfront cash. Under the collaboration, targets were designated as either profit-share programs or royalty-bearing programs.
Corporate History Antigenics L.L.C. was formed as a Delaware limited liability company in 1994 and was converted to Antigenics Inc., a Delaware corporation, in February 2000 in conjunction with our initial public offering of common stock. On January 6, 2011, we changed our name from Antigenics Inc. to Agenus Inc.
Corporate History Antigenics L.L.C. was formed as a Delaware limited liability company in 1994 and converted to Antigenics Inc., a Delaware corporation, in February 2000 in connection with our initial public offering. On January 6, 2011, we changed our name from Antigenics Inc. to Agenus Inc. Availability of Pe riodic SEC Reports Our Internet website address is www.agenusbio.com.
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.
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 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.
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.
Our Subsidiary Companies In October 2021, we completed the initial public offering (“IPO”) of MiNK, which trades on the Nasdaq Capital Market under the ticker symbol “INKT.” MiNK is a clinical stage biopharmaceutical company focused on developing allogeneic iNKT cell therapies to treat cancer and other life-threatening immune diseases.
Equity Investment in MiNK and Subsidiary SaponiQx MiNK Therapeutics In October 2021, MiNK completed its initial public offering and its common stock trades on The Nasdaq Capital Market under the symbol "INKT." MiNK is a clinical-stage biopharmaceutical company focused on developing allogeneic invariant natural killer T (iNKT) cell therapies to treat cancer and other life-threatening immune diseases.
In April 2023, BOT in combination with BAL received Fast Track designation from the U.S. Food and Drug Administration (“FDA”) for the treatment of patients with non-microsatellite instability-high (“MSI-H”) and/or deficient mismatch repair (“dMMR”) metastatic colorectal cancer without active liver involvement.
Refractory MSS Metastatic Colorectal Cancer In April 2023, BOT in combination with BAL received Fast Track designation from the FDA for the treatment of patients with non-microsatellite instability-high (“MSI-H”) and/or deficient mismatch repair (“dMMR”) metastatic colorectal cancer without active liver involvement. We completed enrollment in our Phase 1 study in this population in October 2023.
These two studies of BOT/BAL combination suggest a potential to improve outcomes for patients with early-stage colorectal cancer with the potential to improve recurrence free survival and overall survival while de-escalating the need for chemotherapy, radiotherapy, and surgery in selected patients resulting in organ preservation and improved long term quality of life.
Collectively, these two studies of the BOT plus BAL combination suggest the potential to improve outcomes for patients with early-stage colorectal cancer. The results indicate a possible improvement in recurrence-free survival and overall survival, while also creating the potential to de-escalate the need for chemotherapy, radiotherapy, and surgery in selected patients.
Pursuant to the terms of the license agreement, Ludwig granted us an exclusive, worldwide license under certain intellectual property rights of Ludwig and Memorial Sloan Kettering Cancer Center arising from the prior agreement to further develop and commercialize GITR, OX40 and TIM-3 antibodies.
(“Ludwig”) that replaced and superseded a prior agreement between the parties executed in May 2011. Under this agreement, Ludwig granted us an exclusive, worldwide license to certain intellectual property rights held by Ludwig and Memorial Sloan Kettering Cancer Center arising from the prior agreement to further develop and commercialize GITR, OX40, and TIM-3 antibodies.
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.
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.
Targets under the collaboration were designated as either profit-share programs, where the parties shared all costs and profits equally, or royalty-bearing programs, where Incyte funded all costs, and we were eligible to receive milestones and royalties.
For profit-share programs, the parties shared all costs and profits equally. For royalty-bearing programs, Incyte funded all development costs, and we were eligible to receive milestones and royalties. Under the original agreement, programs targeting GITR, OX40, and two undisclosed targets were designated as profit-share programs, while the remaining targets were royalty-bearing programs.
Pursuant to the terms of the XOMA Royalty Purchase Agreement, XOMA US paid us $15.0 million at closing in exchange for the right to receive 33% of the future royalties and 10% of the future milestones that we were then entitled to receive from Incyte and Merck, net of certain of our obligations to a third party.
XOMA paid us $15.0 million in exchange for the right to receive 33% of certain future royalties and 10% of certain future milestones then payable to us under our Incyte and Merck agreements, net of specified third-party obligations.
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.
There is no guarantee that our antibody product candidates will successfully compete with our competitors’ antibody products and product candidates.
Incyte terminated the OX40 program, effective October 2023, and both the GITR program and undisclosed program, effective May 2024. Upon termination, the rights to the OX40, GITR, and undisclosed programs were returned to us.
Incyte terminated the OX40 program effective October 2023 and terminated both the GITR program and the undisclosed program effective May 2024. Upon termination, the rights to the OX40, GITR, and undisclosed programs were returned to us. In July 2024, Incyte announced it would discontinue further development of the LAG-3 and TIM-3 monoclonal antibodies.
The synthetic royalty can increase by 1% based on the occurrence of certain future events.
In addition, the synthetic royalty may increase by 1% upon the occurrence of certain future events.
Pursuant to the BMS License Agreement, we received a non-refundable upfront cash payment of $200.0 million and were eligible to receive development, regulatory and commercial milestone payments plus royalties on worldwide net sales of products containing AGEN1777.
We received a non-refundable upfront payment of $200.0 million and were eligible for development, regulatory and commercial milestones plus royalties on worldwide net sales.
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.
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.
The combination was well tolerated; no grade 4 events, no unresolved immune-mediated adverse events (“imAEs”), and no surgery delays occurred due to imAEs. The UNICORN Phase 2 study is evaluating pre-operative BOT/BAL combination treatment in resectable colon cancer.
The combination therapy was well tolerated, with no grade 4 events, no unresolved imAEs, and no surgery delays due to imAEs. The UNICORN Phase 2 study is evaluating pre-operative BOT plus BAL combination treatment in resectable colon cancer. Pathological complete and major responses ("pMR") were observed in both pMMR/MSS and dMMR/MSI-H tumors.
MiNK’s most advanced product candidate, agenT-797, is an off-the-shelf, allogeneic, native iNKT cell therapy. Expansion of clinical programs is currently underway, notably a Phase 2 clinical trial in 2L gastric cancer at Memorial Sloan Kettering Cancer Center. MiNK is also evaluating agenT-797 as a variant-agnostic therapy for patients with viral acute respiratory distress syndrome (“ARDS”).
MiNK's most advanced product candidate, agenT-797, is an off-the-shelf, allogeneic native iNKT cell therapy. MiNK is expanding clinical programs, including a Phase 2 trial in second-line gastric cancer at Memorial Sloan Kettering Cancer Center, and is also evaluating agenT-797 in viral acute respiratory distress syndrome and graft-versus-host disease. In July 2025, our ownership percentage of MiNK dropped below 50%.
QS-21 STIMULON Manufacturing Except in the case of GSK, we have retained worldwide manufacturing rights for QS-21 STIMULON, and we have the right to subcontract manufacturing for QS-21 STIMULON.
QS-21 STIMULON Manufacturing Except in the case of GSK, we have retained worldwide manufacturing rights for QS-21 STIMULON and the right to subcontract manufacturing for QS-21 STIMULON. Intellectual Property Portfolio We seek to protect our technologies through a combination of patents, trade secrets and know-how.
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.
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.
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.
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.
We also own, co-own or have exclusive rights to at least 35 pending United States patent applications and at least 180 pending foreign patent applications.
As of the date of this report, we own, co-own or have exclusive rights to at least 44 issued United States patents and at least 300 issued foreign patents. We also own, co-own or have exclusive rights to at least 40 pending United States patent applications and at least 200 pending foreign patent applications.
In 2024 Merck notified us that the further clinical development of MK-4830 will be limited to a neoadjuvant ovarian study of MK-4830 in combination with pembrolizumab and chemotherapy with or without bevacizumab that is ongoing.
Merck is responsible for all future product development expenses for MK-4830, and we remain eligible to receive additional milestone payments and royalties on any future sales. In 2024, Merck notified us that further clinical development of MK-4830 would be limited to an ongoing neoadjuvant ovarian study in combination with pembrolizumab and chemotherapy with or without bevacizumab.
Human Capital Resources and Emplo yees As of February 28, 2025, we had 316 employees, of whom 68 were PhDs and 17 were MDs. None of our employees are subject to a collective bargaining agreement. We believe that we have good relations with our employees.
Human Capital Resources and Emplo yees As of February 28, 2026, we had 81 employees, of whom 19 held Ph.D. degrees and 5 held M.D. degrees. None of our employees are subject to a collective bargaining agreement, and we believe that our employee relations are constructive.
The randomized, global Phase 2 trial (n=234) investigated BOT/BAL in refractory MSS mCRC NLM vs standard treatments (regorafenib or trifluridine/tipiracil). In July 2024, we conducted an End-of-Phase-2 meeting with the FDA for this program.
These data informed the design of our randomized, global Phase 2 study (n=234), which compared BOT plus BAL against standard treatments (regorafenib or trifluridine/tipiracil) in refractory MSS mCRC without active liver metastases. In July 2024, we held an end-of-Phase 2 meeting with the FDA.
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 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: 10 1.
Serious adverse events (“AEs”) were reported in 16% of patients, with treatment-related AEs in 5%, and only one surgery delayed due to an adverse event..
Patients with dMMR/MSI-H tumors achieved a 93% pCR and 100% pMR, while patients with pMMR/MSS colorectal cancer had a 29% pCR and 36% pMR rate. Serious adverse events (“AEs”) were reported in 16% of patients, with treatment-related AEs in 5%, and only one surgery was delayed due to an adverse event.
In 2009, we entered into an Amended and Restated Manufacturing Technology Transfer and Supply Agreement (the “Amended GSK Supply Agreement”) under which GSK has the right to manufacture all of its requirements of commercial grade QS-21 STIMULON.
In 2009, we entered into an amended and restated technology transfer and supply agreement under which GSK obtained the right to manufacture all of its commercial grade QS-21 requirements. In 2012, we amended the agreements to clarify and expand certain rights and received a $9.0 million upfront payment, $2.5 million of which was creditable against future royalties.
Safety findings were consistent with prior data, with no new safety signals or treatment-related deaths observed. The most common immune-mediated adverse events (“imAEs”) at BOT75mg + BAL included diarrhea/colitis and hypothyroidism, all grades, 35% and 13%, respectively.
The most common immune-mediated adverse events (“imAEs”) at BOT 75mg plus BAL included diarrhea/colitis and hypothyroidism, all grades, 35% and 13%, respectively.
These sources may be competitive to our ability to execute future partnering and licensing arrangements involving QS-21 STIMULON. We 12 are also aware of other manufacturers 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.
In some instances, we may obtain later-expiring patents relating to our products directed to particular forms or compositions, to methods of manufacturing, or to use of the drug in the treatment of particular diseases or conditions.
In some cases, we may obtain later-expiring patents relating to our products that cover particular forms or compositions, manufacturing methods, or the use of the drug to treat specific diseases or conditions. However, such patents may not, in all cases, protect our products from generic or, where applicable, biosimilar competition after the expiration of the basic patent.
Ligand In May 2024, we, and certain of our wholly-owned subsidiaries, entered into a Purchase and Sale Agreement (the “Ligand Purchase Agreement”) with Ligand Pharmaceuticals Incorporated (“Ligand”) for the sale to Ligand of (i) 31.875% of the 6 development, regulatory and commercial milestone payments we were then eligible to receive under our agreements with BMS, UroGen, Gilead, Merck and Incyte (the “Covered License Agreements”); (ii) 18.75% of the royalties we receive under the Covered License Agreements; and (iii) a 2.625% synthetic royalty on worldwide net sales of BOT and BAL (collectively the “Purchased Assets”).
Under that agreement, Ligand acquired (i) 31.875% of the development, regulatory and commercial milestones then payable to us under agreements with BMS, UroGen, Gilead, Merck and Incyte, (ii) 18.75% of the royalties under those agreements and (iii) a 2.625% synthetic royalty on worldwide net sales of BOT and BAL.
Under the terms of the Agreement, we are generally entitled to receive a 2% royalty on net sales of prophylactic vaccines for a period of 10 years after the first commercial sale of a resulting GSK product, which was triggered with GSK’s first commercial sale of Shingrix in 2017.
Under the GSK agreements, we are generally entitled to a 2% royalty on net sales of prophylactic vaccines for a period of 10 years after the first commercial sale of a resulting GSK product; however, we are no longer entitled to any additional milestone payments under those agreements and we have monetized and sold the entire royalty stream associated with GSK’s vaccine products containing QS-21 STIMULON, including Shingrix and Arexvy.
In addition to salaries, these programs include potential annual discretionary bonuses, various stock awards under our equity incentive plans, a 401(k) Plan, healthcare and insurance benefits, flexible spending accounts, paid time off, family leave, and flexible work schedules, among others.
We offer competitive compensation and benefit programs designed to support these objectives, including base salary, discretionary annual bonuses, equity-based compensation, a 401(k) plan, health and insurance benefits, flexible spending accounts, paid time off, family leave and flexible work arrangements, among others.
The study highlights SaponiQx’s innovative cpcQS-21 adjuvant technology. Partnered QS-21 STIMULON Programs In 2006, we entered into a license agreement and a supply agreement with GSK for the use of QS-21 STIMULON (the “GSK License Agreement” and the “GSK Supply Agreement,” respectively).
Historically, QS-21 has been purified from the bark of the Chilean soapbark tree, Quillaja. Partnered QS-21 STIMULON Programs In 2006, we entered into a license agreement and a supply agreement with GlaxoSmithKline Biologicals, S.A. ("GSK") for the use of QS-21 STIMULON.
Patent term extensions, supplementary protection certificates, and regulatory exclusivity periods, including pediatric exclusivity periods are not reflected in the expiration dates listed in the table below.
Unless otherwise indicated, the years shown in the table represent the expiration dates of the basic product patents for the respective products. The listed expiration dates do not reflect potential patent term extensions, supplementary protection certificates, or regulatory exclusivity periods, including pediatric exclusivity.
In March 2022, we received a $5.0 million clinical milestone under the AGEN2373 option agreement. In August 2024, Gilead elected not to exercise the option to license AGEN2373 and the option and license agreement was formally terminated. Incyte In January 2015, we entered into a collaboration with Incyte to discover, develop and commercialize novel immuno-therapeutics using our antibody platforms.
In July 2024, BMS notified us that it was voluntarily terminating the license agreement effective January 26, 2025, and rights to AGEN1777 were returned to us. Incyte In January 2015, we entered into a collaboration with Incyte to discover, develop, and commercialize novel immuno-therapeutics using our antibody platforms.
The FDA agreed on a Phase 3 dosing regimen of 75mg BOT every six weeks (up to four doses) combined with 240mg BAL every two weeks (up to two years). However, the FDA advised against pursuing accelerated approval based on the current data, suggesting that objective response rates may not directly translate to a survival benefit.
The FDA agreed on a Phase 3 dosing regimen of 75 mg of BOT every six weeks (up to four doses) in combination with 240 mg of BAL every two weeks (up to two years).
Balstilimab (BAL) 3 is a novel, fully human monoclonal immunoglobulin G4 (IgG4) PD-1 (programmed cell death protein 1) inhibitor. It is designed to block PD-1 from interacting with its ligands PD-L1 and PD-L2, enhance T cell activation and effector function BAL is designed to block PD-1 and reactivate exhausted T cells, restoring their ability to fight cancer.
Balstilimab is a fully human monoclonal immunoglobulin G4 (IgG4) anti-PD-1 antibody designed to block PD-1 from interacting with PD-L1 and PD-L2.
However, in some cases, such patents may not protect our drug from generic or, as applicable, biosimilar competition after the expiration of the basic patent. Projected Patent Expiration Year on a Candidate by Candidate Basis Candidate U.S. Basic Product Patent Expiration Year (Earliest Estimated Year) E.U.
Projected Patent Expiration Year on a Candidate by Candidate Basis Candidate U.S. Basic Product Patent Expiration Year (Earliest Estimated Year) E.U.

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Item 1A. Risk Factors

Risk Factors — what could go wrong, per management

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Biggest changeRisks Related to Government Regulation • The regulatory approval process for our product candidates is uncertain and will be lengthy, and may evolve even after we have engaged with relevant regulatory authorities and selected a regulatory pathway. • We may fail to obtain regulatory approval of our product candidates. • Our business operations and relationships with third parties are subject to extensive healthcare laws and regulations. • If we receive regulatory approval of any product candidates or therapies, we will be subject to ongoing regulatory obligations and continued regulatory review to maintain the approval. • Healthcare reform initiatives may have an adverse effect on our business. • Laws and regulations governing any international operations may preclude us from developing, manufacturing and selling certain products outside of the United States and require us to develop and implement costly compliance programs. • Risks associated with doing business internationally could negatively affect our business. • Our ability to use net operating losses and tax credits to offset future income may be subject to limitations.
Biggest changeRisks Related to Our Reliance on Third Parties • We are dependent upon third parties to further develop and commercialize certain of our antibody programs. • Failure to enter into and/or maintain clinical trial, licensing, distribution and/or collaboration agreements may adversely affect our business. • If third parties do not carry out their contractual duties, we may not be able to obtain regulatory approval of or commercialize any potential product candidates. 13 Risks Related to Government Regulation • The regulatory approval process for our product candidates is uncertain and will be lengthy, and may evolve even after we have engaged with relevant regulatory authorities and selected a regulatory pathway. • We may fail to obtain regulatory approval of our product candidates. • Our business operations and relationships with third parties are subject to extensive healthcare laws and regulations. • If we receive regulatory approval of any product candidates or therapies, we will be subject to ongoing regulatory obligations and continued regulatory review to maintain the approval. • Healthcare reform initiatives may have an adverse effect on our business. • Laws and regulations governing any international operations may preclude us from developing, manufacturing and selling certain products outside of the United States and require us to develop and implement costly compliance programs. • Risks associated with doing business internationally could negatively affect our business. • Our ability to use net operating losses and tax credits to offset future income may be subject to limitations. • Our use of new and evolving technologies, such as artificial intelligence, or AI, may present risks and challenges that can impact our business Risks Related to Our Intellectual Property • We may be unable to obtain and enforce patent protection for our product candidates and related technology. • If we fail to comply with our intellectual property licenses, we could lose important license rights. • We may not be able to protect our intellectual property rights throughout the world. • Changes in U.S. patent law could diminish the value of patents. • We may be unable to protect the confidentiality of our proprietary information. • Our employees, consultants or independent contractors could wrongfully use or disclose confidential information. • We may infringe the patents and other proprietary rights of third parties. • We may become involved in lawsuits to protect or enforce our patents.
If we or any of our third-party manufacturers encounter difficulties in manufacturing our product candidates, our ability to provide supply of our product candidates for clinical trials or our products for patients, if approved, could be delayed or stopped, or we may be unable to maintain a commercially viable cost structure.
If any of our third-party manufacturers encounter difficulties in manufacturing our product candidates, our ability to provide supply of our product candidates for clinical trials or our products for patients, if approved, could be delayed or stopped, or we may be unable to maintain a commercially viable cost structure.
If microbial, viral, or other contaminations are discovered in our product candidates or in our manufacturing facilities in which our product candidates are made, production at such manufacturing facilities may be interrupted for an extended period of time to investigate and remedy the contamination.
If microbial, viral, or other contaminations are discovered in our product candidates or in the manufacturing facilities in which our product candidates are made, production at such manufacturing facilities may be interrupted for an extended period of time to investigate and remedy the contamination.
In addition, the government may assert that a claim including items and services resulting from a violation of the federal anti-kickback statute constitutes a false or fraudulent claim for the purposes of the FCA; • the federal civil monetary penalties laws, which impose civil fines for, among other things, the offering or transfer of remuneration to a Medicare state healthcare program beneficiary if the person knows or should know it is likely to influence the beneficiary’s selection of a particular provider, practitioner, or supplier of services reimbursable by a Medicare or a state healthcare program; • the federal Health Insurance Portability and Accountability Act of 1996 (“HIPAA”), as amended, which imposes criminal and civil liability for executing a scheme to defraud any healthcare benefit program, including private health plans, and also establishes requirements related to the privacy security, and transmission or individually identifiable health information which apply to many healthcare providers, physicians and third-party payors with whom we interact; • the federal false statement statute prohibits knowingly and willfully falsifying, concealing or covering up a material fact or making any materially false statement in connection with the delivery of, or payment for healthcare benefits, items or services; • the federal anti-kickback prohibition known as Eliminating Kickbacks in Recovery Act, or EKRA, which prohibits certain payments related to referrals of patients to certain providers (recovery homes, clinical treatment facilities, and laboratories) and applies to services reimbursed by private health plans as well as government health care programs; • the FDCA, which, among other things, strictly regulates drug product and medical device marketing, prohibits manufacturers from marketing such products for off-label use and regulates the distribution of samples; • federal laws, such as the Medicaid Drug Rebate Program, that require pharmaceutical manufacturers to calculate, report and certify certain complex product prices to the government or provide certain discounts or rebates to government authorities or private entities, often as a condition of reimbursement under governmental healthcare programs; • federal and state consumer protection and unfair competition laws, which broadly regulate marketplace activities and activities that potentially harm consumers; • the so-called federal “sunshine law” or Open Payments which requires manufacturers of drugs, devices, biologics and medical supplies to report to the Centers for Medicare & Medicaid Services information related to payments and other “transfers of value” to teaching hospitals, physicians and other healthcare practitioners, as well as ownership and investment interests held by physicians and their immediate family members; and • analogous state laws and regulations, such as state anti-kickback and false claims laws, which may apply to sales or marketing arrangements and claims involving healthcare items or services reimbursed by non-governmental third-party payors, including private health plans, and state laws which regulate interaction between pharmaceutical companies and healthcare providers, require pharmaceutical companies to comply with specific compliance standards, require 41 pharmaceutical companies to report information on transfers of value to other healthcare providers, marketing expenditures; or pricing information and/or require licensing of sales representatives.
In addition, the government may assert that a claim including items and services resulting from a violation of the federal anti-kickback statute constitutes a false or fraudulent claim for the purposes of the FCA; • the federal civil monetary penalties laws, which impose civil fines for, among other things, the offering or transfer of remuneration to a Medicare state healthcare program beneficiary if the person knows or should know it is likely to influence the beneficiary’s selection of a particular provider, practitioner, or supplier of services reimbursable by a Medicare or a state healthcare program; • the federal Health Insurance Portability and Accountability Act of 1996 (“HIPAA”), as amended, which imposes criminal and civil liability for executing a scheme to defraud any healthcare benefit program, including private health plans, and also establishes requirements related to the privacy security, and transmission or individually identifiable health information which apply to many healthcare providers, physicians and third-party payors with whom we interact; • the federal false statement statute prohibits knowingly and willfully falsifying, concealing or covering up a material fact or making any materially false statement in connection with the delivery of, or payment for healthcare benefits, items or services; • the federal anti-kickback prohibition known as Eliminating Kickbacks in Recovery Act, or EKRA, which prohibits certain payments related to referrals of patients to certain providers (recovery homes, clinical treatment facilities, and laboratories) and applies to services reimbursed by private health plans as well as government health care programs; • the FDCA, which, among other things, strictly regulates drug product and medical device marketing, prohibits manufacturers from marketing such products for off-label use and regulates the distribution of samples; • federal laws, such as the Medicaid Drug Rebate Program, that require pharmaceutical manufacturers to calculate, report and certify certain complex product prices to the government or provide certain discounts or rebates to government authorities or private entities, often as a condition of reimbursement under governmental healthcare programs; • federal and state consumer protection and unfair competition laws, which broadly regulate marketplace activities and activities that potentially harm consumers; • the so-called federal “sunshine law” or Open Payments which requires manufacturers of drugs, devices, biologics and medical supplies to report to the Centers for Medicare & Medicaid Services information related to payments and other “transfers of value” to teaching hospitals, physicians and other healthcare practitioners, as well as ownership and investment interests held by physicians and their immediate family members; and • analogous state laws and regulations, such as state anti-kickback and false claims laws, which may apply to sales or marketing arrangements and claims involving healthcare items or services reimbursed by non-governmental third-party payors, including private health plans, and state laws which regulate interaction between pharmaceutical companies and healthcare providers, require pharmaceutical companies to comply with specific compliance standards, require pharmaceutical companies to report information on transfers of value to other healthcare providers, marketing expenditures; or pricing information and/or require licensing of sales representatives.
Any licensing, distribution and/or collaborations agreements, we enter into, may pose a number of risks, including the following: • collaborators have significant discretion in determining the efforts and resources that they will apply; • collaborators may not perform their obligations as expected; • collaborators may not pursue development and commercialization of any product candidates that achieve regulatory approval or may elect not to continue or renew development or commercialization programs or license arrangements based on clinical trial results, changes in the collaborators’ strategic focus or available funding, or external factors, such as a strategic transaction that may divert resources or create competing priorities; • collaborators may delay clinical trials, provide insufficient funding for a clinical trial program, stop a clinical trial or abandon a product candidate, repeat or conduct new clinical trials or require a new formulation of a product candidate for clinical testing; • collaborators could independently develop, or develop with third parties, products that compete directly or indirectly with our products and product candidates if the collaborators believe that the competitive products are more likely to be successfully developed or can be commercialized under terms that are more economically attractive than ours; • product candidates discovered in collaboration with us may be viewed by our collaborators as competitive with their own product candidates or products, which may cause collaborators to cease to devote resources to the commercialization of our product candidates; • collaborators may fail to comply with applicable regulatory requirements regarding the development, manufacture, distribution or marketing of a product candidate or product; • collaborators with marketing and distribution rights to one or more of our product candidates that achieve regulatory approval may not commit sufficient resources to the marketing and distribution of such product or products; • disagreements with collaborators, including disagreements over proprietary rights, contract interpretation or the preferred course of development, might cause delays or terminations of the research, development or commercialization of product candidates, might lead to additional responsibilities for us with respect to product candidates, or might result in litigation or arbitration, any of which would be time-consuming and expensive; 36 • collaborators may not properly maintain or defend our intellectual property rights or may use our proprietary information in such a way as to invite litigation that could jeopardize or invalidate our intellectual property or proprietary information or expose us to potential litigation; • collaborators may infringe the intellectual property rights of third parties, which may expose us to litigation and potential liability; • if a collaborator of ours is involved in a business combination, the collaborator might deemphasize or terminate the development or commercialization of any product candidate licensed to it by us; and • collaborations may be terminated by the collaborator, and, if terminated, we could be required to raise additional capital to pursue further development or commercialization of the applicable product candidates.
Any licensing, distribution and/or collaborations agreements, we enter into, may pose a number of risks, including the following: • collaborators have significant discretion in determining the efforts and resources that they will apply; • collaborators may not perform their obligations as expected; • collaborators may not pursue development and commercialization of any product candidates that achieve regulatory approval or may elect not to continue or renew development or commercialization programs or license arrangements based on clinical trial results, changes in the collaborators’ strategic focus or available funding, or external factors, such as a strategic transaction that may divert resources or create competing priorities; • collaborators may delay clinical trials, provide insufficient funding for a clinical trial program, stop a clinical trial or abandon a product candidate, repeat or conduct new clinical trials or require a new formulation of a product candidate for clinical testing; • collaborators could independently develop, or develop with third parties, products that compete directly or indirectly with our products and product candidates if the collaborators believe that the competitive products are more likely to be successfully developed or can be commercialized under terms that are more economically attractive than ours; • product candidates discovered in collaboration with us may be viewed by our collaborators as competitive with their own product candidates or products, which may cause collaborators to cease to devote resources to the commercialization of our product candidates; • collaborators may fail to comply with applicable regulatory requirements regarding the development, manufacture, distribution or marketing of a product candidate or product; • collaborators with marketing and distribution rights to one or more of our product candidates that achieve regulatory approval may not commit sufficient resources to the marketing and distribution of such product or products; • disagreements with collaborators, including disagreements over proprietary rights, contract interpretation or the preferred course of development, might cause delays or terminations of the research, development or commercialization of product candidates, might lead to additional responsibilities for us with respect to product candidates, or might result in litigation or arbitration, any of which would be time-consuming and expensive; • collaborators may not properly maintain or defend our intellectual property rights or may use our proprietary information in such a way as to invite litigation that could jeopardize or invalidate our intellectual property or proprietary information or expose us to potential litigation; • collaborators may infringe the intellectual property rights of third parties, which may expose us to litigation and potential liability; • if a collaborator of ours is involved in a business combination, the collaborator might deemphasize or terminate the development or commercialization of any product candidate licensed to it by us; and • collaborations may be terminated by the collaborator, and, if terminated, we could be required to raise additional capital to pursue further development or commercialization of the applicable product candidates.
Our product candidates could be delayed in receiving, or fail to receive, regulatory approval for many reasons, including the following: • the FDA or comparable foreign regulatory authorities may disagree with the design or implementation of our clinical trials; • we may be unable to demonstrate to the satisfaction of the FDA or comparable foreign regulatory authorities that a product candidate is safe , pure and potent and has a favorable risk-benefit profile for its proposed indication; • the FDA or comparable foreign regulatory authorities may require us to obtain clearance or approval of a companion diagnostic; • the results of clinical trials may not meet the level of statistical significance required by the FDA or comparable foreign regulatory authorities for approval; • we may be unable to demonstrate that a product candidate’s clinical and other benefits outweigh its safety risks; • the FDA or comparable foreign regulatory authorities may disagree with our interpretation of data from preclinical studies or clinical trials; • The FDA or comparable foreign regulatory authorities may disagree with our selected dosing regimen or regimens or determine that additional data are needed to support dose selection; • the regulatory pathway being pursued is eliminated due to the unexpected or early full approval of a competing agent, as occurred with balstilimab; 25 • the data collected from clinical trials of our product candidates may not be sufficient to support the submission of an BLA or other submission or to obtain regulatory approval in the United States or elsewhere; • the FDA or comparable foreign regulatory authorities may fail to approve our manufacturing processes or facilities or those of our third-party manufacturers with which we contract for clinical and commercial supplies; and • the approval standard policies or regulations of the FDA or comparable foreign regulatory authorities may significantly change in a manner rendering our clinical data insufficient for approval.
Our product candidates could be delayed in receiving, or fail to receive, regulatory approval for many reasons, including the following: • the FDA or comparable foreign regulatory authorities may disagree with the design or implementation of our clinical trials; • we may be unable to demonstrate to the satisfaction of the FDA or comparable foreign regulatory authorities that a product candidate is safe, pure and potent and has a favorable risk-benefit profile for its proposed indication; • the FDA or comparable foreign regulatory authorities may require us to obtain clearance or approval of a companion diagnostic; • the results of clinical trials may not meet the level of statistical significance required by the FDA or comparable foreign regulatory authorities for approval; • we may be unable to demonstrate that a product candidate’s clinical and other benefits outweigh its safety risks; • the FDA or comparable foreign regulatory authorities may disagree with our interpretation of data from preclinical studies or clinical trials; • The FDA or comparable foreign regulatory authorities may disagree with our selected dosing regimen or regimens or determine that additional data are needed to support dose selection; • the regulatory pathway being pursued is eliminated due to the unexpected or early full approval of a competing agent, as occurred with balstilimab; • the data collected from clinical trials of our product candidates may not be sufficient to support the submission of an BLA or other submission or to obtain regulatory approval in the United States or elsewhere; • the FDA or comparable foreign regulatory authorities may fail to approve our manufacturing processes or facilities or those of our third-party manufacturers with which we contract for clinical and commercial supplies; and • the approval standard policies or regulations of the FDA or comparable foreign regulatory authorities may significantly change in a manner rendering our clinical data insufficient for approval.
Our future funding requirements, both near and long-term, will depend on many factors, including, but not limited to: • the initiation, progress, timing, costs and results of preclinical or nonclinical testing and studies and clinical trials for our product candidates; • the clinical development plans we establish for our product candidates; • the number and characteristics of future product candidates that we develop or may in-license; 16 • our ability to establish and maintain strategic partnerships, licensing or other arrangements and the financial terms of such arrangements; • the timing, receipt and amount of sales of, or royalties on, our future products and those of our partners, if any; • the outcome, timing and cost of meeting regulatory requirements established by the FDA, the EMA and other comparable foreign regulatory authorities; • the cost of filing, prosecuting, defending and enforcing our patent claims and other intellectual property rights; • the cost of defending intellectual property disputes, including patent infringement actions brought by third parties against us or our product candidates; • the effect of competing technological and market developments; • the costs of establishing and maintaining a clinical and commercial supply chain for the development and manufacture of our product candidates; • the cost and timing of establishing, expanding and scaling commercial manufacturing capabilities; and • the cost of establishing sales, marketing and distribution capabilities for any product candidates for which we may receive regulatory approval in regions where we choose to commercialize our products on our own.
Our future funding requirements, both near and long-term, will depend on many factors, including, but not limited to: • the initiation, progress, timing, costs and results of preclinical or nonclinical testing and studies and clinical trials for our product candidates; • the clinical development plans we establish for our product candidates; • the number and characteristics of future product candidates that we develop or may in-license; • our ability to establish and maintain strategic partnerships, licensing or other arrangements and the financial terms of such arrangements; • the timing, receipt and amount of sales of, or royalties on, our future products and those of our partners, if any; • the outcome, timing and cost of meeting regulatory requirements established by the FDA, the EMA and other comparable foreign regulatory authorities; • the cost of filing, prosecuting, defending and enforcing our patent claims and other intellectual property rights; • the cost of defending intellectual property disputes, including patent infringement actions brought by third parties against us or our product candidates; • the effect of competing technological and market developments; • the costs of establishing and maintaining a clinical and commercial supply chain for the development and manufacture of our product candidates; • the cost and timing of establishing, expanding and scaling commercial manufacturing capabilities; and • the cost of establishing sales, marketing and distribution capabilities for any product candidates for which we may receive regulatory approval in regions where we choose to commercialize our products on our own.
Among other things, such delays may be caused by slow enrollment in clinical trials, patients dropping out of trials, length of time to achieve trial endpoints, additional time requirements for data analysis, or BLA preparation, disagreement with the FDA regarding clinical trial design or our interpretation of data,, an FDA request for additional nonclinical or clinical data that may be deemed necessary to meet evolving regulatory standards and pathways, other discussions with FDA, or unexpected safety or manufacturing issues; • clinical and commercial manufacturing costs, formulation issues, pricing or reimbursement issues, or other factors that make the candidates uneconomical; • proprietary rights of others and their competing products and technologies that may prevent our candidates from being commercialized or profitable; 21 • failure to initiate or successfully complete confirmation trials for candidates that receive accelerated approval; and • the length of time necessary to complete clinical trials and to submit an application for marketing approval for a final decision by a regulatory authority may be difficult to predict for immune modulating antibodies, including for CTLA-4 antibody and related combination therapies.
Among other things, such delays may be caused by slow enrollment in clinical trials, patients dropping out of trials, length of time to achieve trial endpoints, additional time requirements for data analysis, or BLA preparation, disagreement with the FDA regarding clinical trial design or our interpretation of data,, an FDA request for additional nonclinical or clinical data that may be deemed necessary to meet evolving regulatory standards and pathways, other discussions with FDA, or unexpected safety or manufacturing issues; • clinical and commercial manufacturing costs, formulation issues, pricing or reimbursement issues, or other factors that make the candidates uneconomical; • proprietary rights of others and their competing products and technologies that may prevent our candidates from being commercialized or profitable; • failure to initiate or successfully complete confirmation trials for candidates that receive accelerated approval; and • the length of time necessary to complete clinical trials and to submit an application for marketing approval for a final decision by a regulatory authority may be difficult to predict for immune modulating antibodies, including for CTLA-4 antibody and related combination therapies.
If one or more of our product candidates receives regulatory approval, and we, or others, later discover that they are less effective than previously believed, or cause undesirable side effects, a number of potentially significant negative consequences could result, including: • withdrawal or limitation by regulatory authorities of approvals of such product; • seizure of the product by regulatory authorities; • recall of the product; • restrictions on the marketing of the product or the manufacturing process for any component thereof; • requirement by regulatory authorities of additional warnings on the label, such as a “black box” warning or contraindication; • requirement that we implement a REMS or create a medication guide outlining the risks of such side effects for distribution to patients; • commitment to expensive additional safety studies prior to approval or post-marketing studies required by regulatory authorities of such product; • the product may become less competitive; • initiation of regulatory investigations and government enforcement actions; • initiation of legal action against us to hold us liable for harm caused to patients; and • harm to our reputation and resulting harm to physician or patient acceptance of our products.
If one or more of our product candidates receives regulatory approval, and we, or others, later discover that they are less effective than previously believed, or cause undesirable side effects, a number of potentially significant negative consequences could result, including: • withdrawal or limitation by regulatory authorities of approvals of such product; • seizure of the product by regulatory authorities; • recall of the product; • restrictions on the marketing of the product or the manufacturing process for any component thereof; • requirement by regulatory authorities of additional warnings on the label, such as a “black box” warning or contraindication; 28 • requirement that we implement a REMS or create a medication guide outlining the risks of such side effects for distribution to patients; • commitment to expensive additional safety studies prior to approval or post-marketing studies required by regulatory authorities of such product; • the product may become less competitive; • initiation of regulatory investigations and government enforcement actions; • initiation of legal action against us to hold us liable for harm caused to patients; and • harm to our reputation and resulting harm to physician or patient acceptance of our products.
The types of situations in which we may become a party to such litigation or proceedings include: • we or our collaborators may initiate litigation or other proceedings against third parties seeking to invalidate the patents held by those third parties or to obtain a judgment that our products or processes do not infringe those third parties’ patents; • if our competitors file patent applications that claim technology also claimed by us or our licensors or licensees, we or our licensors or licensees may be required to participate in interference, derivation or other proceedings to determine the 54 priority of invention, which could jeopardize our patent rights and potentially provide a third party with a dominant patent position; • if third parties initiate litigation claiming that our processes or products infringe their patent or other intellectual property rights, we and our collaborators will need to defend against such proceedings; and • if a license to necessary technology is terminated, the licensor may initiate litigation claiming that our processes or products infringe or misappropriate their patent or other intellectual property rights and/or that we breached our obligations under the license agreement, and we and our collaborators would need to defend against such proceedings.
The types of situations in which we may become a party to such litigation or proceedings include: • we or our collaborators may initiate litigation or other proceedings against third parties seeking to invalidate the patents held by those third parties or to obtain a judgment that our products or processes do not infringe those third parties’ patents; • if our competitors file patent applications that claim technology also claimed by us or our licensors or licensees, we or our licensors or licensees may be required to participate in interference, derivation or other proceedings to determine the priority of invention, which could jeopardize our patent rights and potentially provide a third party with a dominant patent position; • if third parties initiate litigation claiming that our processes or products infringe their patent or other intellectual property rights, we and our collaborators will need to defend against such proceedings; and • if a license to necessary technology is terminated, the licensor may initiate litigation claiming that our processes or products infringe or misappropriate their patent or other intellectual property rights and/or that we breached our obligations under the license agreement, and we and our collaborators would need to defend against such proceedings.
Risks Related to the Development of Our Product Candidates 13 • Our business is highly dependent on the success of botensilimab and our combination therapy programs. • Preliminary or interim data that we report on our clinical trials could change materially by the time the data is finalized. • Our clinical trials or those of our current and future collaborators may reveal significant adverse events or a lack of therapeutic efficacy or durability of treatment-related effect. • If we encounter difficulties enrolling patients in our clinical trials, our clinical development activities could be delayed or otherwise adversely affected. • We have limited resources, and the number of product candidates that we are attempting to simultaneously advance creates a significant strain on these resources and could prevent us from successfully advancing any candidates.
Risks Related to the Development of Our Product Candidates • Our business is highly dependent on the success of botensilimab and our combination therapy programs. • Preliminary or interim data that we report on our clinical trials could change materially by the time the data is finalized. • Our clinical trials or those of our current and future collaborators may reveal significant adverse events or a lack of therapeutic efficacy or durability of treatment-related effect. • If we encounter difficulties enrolling patients in our clinical trials, our clinical development activities could be delayed or otherwise adversely affected. • We have limited resources, and the number of product candidates that we are attempting to simultaneously advance creates a significant strain on these resources and could prevent us from successfully advancing any candidates.
The degree of market acceptance of any future products, if approved for commercial sale, will depend on a number of factors, including: 29 • the prevalence and severity of the disease; • efficacy and potential advantages compared to alternative treatments; • the ability to offer our products, if approved, for sale at competitive prices; • convenience and ease of administration compared to alternative treatments; • the willingness of the target patient population to try new therapies and of physicians to prescribe these therapies; • the perceived ratio of risk and benefit of these therapies by physicians; • the strength of marketing and distribution support; • sufficient third-party coverage or reimbursement, including of combination therapies; • adoption of a companion diagnostic and/or complementary diagnostic; and • the prevalence and severity of any side effects, including any limitations or warnings contained in a product’s approved labeling.
The degree of market acceptance of any future products, if approved for commercial sale, will depend on a number of factors, including: • the prevalence and severity of the disease; • efficacy and potential advantages compared to alternative treatments; • the ability to offer our products, if approved, for sale at competitive prices; • convenience and ease of administration compared to alternative treatments; • the willingness of the target patient population to try new therapies and of physicians to prescribe these therapies; • the perceived ratio of risk and benefit of these therapies by physicians; • the strength of marketing and distribution support; • sufficient third-party coverage or reimbursement, including of combination therapies; • adoption of a companion diagnostic and/or complementary diagnostic; and • the prevalence and severity of any side effects, including any limitations or warnings contained in a product’s approved labeling.
In addition to general market volatility, many factors may have a significant adverse effect on the market price of our stock, including: • continuing operating losses, which we expect over the next several years if we are able to transition to a commercial organization; • announcements of decisions made by public officials or delays in any such announcements; • results of our pre-clinical studies and clinical trials or delays in anticipated timing; • delays in our regulatory filings or those of our partners; • announcements of new collaboration agreements with strategic partners or developments by our existing collaboration partners; • announcements of acquisitions; • announcements of technological innovations, new commercial products, failures of products, or progress toward commercialization by our competitors or peers; • failure to realize the anticipated benefits of acquisitions; • developments concerning proprietary rights, including patent and litigation matters; 62 • publicity regarding actual or potential results with respect to product candidates under development; • quarterly fluctuations in our financial results, including our average monthly cash used in operating activities; • variations in the level of expenses related to any of our product candidates or clinical development programs; • additions or departures of key management or scientific personnel; • conditions or trends in the biopharmaceutical, biotechnology and pharmaceutical industries generally; • other events or factors, including those resulting from war, incidents of terrorism, natural disasters or responses to these events; • changes in accounting principles; • general economic and market conditions and other factors that may be unrelated to our operating performance or the operating performance of our competitors, including changes in market valuations of similar companies; and • sales of common stock by us or our stockholders in the future, as well as the overall trading volume of our common stock.
In addition to general market volatility, many factors may have a significant adverse effect on the market price of our stock, including: • continuing operating losses, which we expect over the next several years if we are able to transition to a commercial organization; • announcements of decisions made by public officials or delays in any such announcements; • results of our pre-clinical studies and clinical trials or delays in anticipated timing; • delays in our regulatory filings or those of our partners; • announcements of new collaboration agreements with strategic partners or developments by our existing collaboration partners; • announcements of acquisitions; • announcements of technological innovations, new commercial products, failures of products, or progress toward commercialization by our competitors or peers; • failure to realize the anticipated benefits of acquisitions; • developments concerning proprietary rights, including patent and litigation matters; • publicity regarding actual or potential results with respect to product candidates under development; 61 • quarterly fluctuations in our financial results, including our average monthly cash used in operating activities; • variations in the level of expenses related to any of our product candidates or clinical development programs; • additions or departures of key management or scientific personnel; • conditions or trends in the biopharmaceutical, biotechnology and pharmaceutical industries generally; • other events or factors, including those resulting from war, incidents of terrorism, natural disasters or responses to these events; • changes in accounting principles; • general economic and market conditions and other factors that may be unrelated to our operating performance or the operating performance of our competitors, including changes in market valuations of similar companies; and • sales of common stock by us or our stockholders in the future, as well as the overall trading volume of our common stock.
Such laws, some of which may apply only after our products are approved for marketing, include: • the federal healthcare anti-kickback statute, which prohibits, among other things, persons from knowingly and willfully soliciting, offering, receiving, or providing remuneration, directly or indirectly, in cash or in kind, to induce or reward, either the referral of an individual for, or the purchase, order or recommendation of, any good or service for which payment may be made, under federal and state healthcare programs, such as Medicare and Medicaid.
Such laws, some of which may apply only after our products are approved for marketing, include: 39 • the federal healthcare anti-kickback statute, which prohibits, among other things, persons from knowingly and willfully soliciting, offering, receiving, or providing remuneration, directly or indirectly, in cash or in kind, to induce or reward, either the referral of an individual for, or the purchase, order or recommendation of, any good or service for which payment may be made, under federal and state healthcare programs, such as Medicare and Medicaid.
In addition, if a product that has orphan drug designation subsequently receives the first FDA approval for the disease for which it has such designation, the product is entitled to orphan drug exclusivity, which means that the FDA may not approve any other applications, including a full new drug application, or NDA, or BLA, to market the same drug or biologic for the same indication for seven years, except in limited circumstances, such as a showing of clinical superiority to the product with orphan drug exclusivity or where the original manufacturer is unable to assure sufficient product quantity.
In addition, if a product that has orphan drug designation subsequently receives the first FDA approval for the disease for which it has such designation, the product is entitled to orphan drug exclusivity, which means that the FDA may not approve any other applications, including a full new drug application, or NDA, or BLA, to market the same drug or biologic for the same indication for seven years, except in limited 38 circumstances, such as a showing of clinical superiority to the product with orphan drug exclusivity or where the original manufacturer is unable to assure sufficient product quantity.
As described above under “Risk factors—Risks Related to Our Financial Position and Need for Additional Capital,” we have incurred significant net losses since our inception and anticipate that we will continue to incur significant losses for the foreseeable future; and therefore, we do not know whether or when we will generate the U.S. federal or state taxable income 48 necessary to utilize our NOLs or credits that are subject to limitation by Sections 382 and 383 of the Code.
As described above under “Risk factors—Risks Related to Our Financial Position and Need for Additional Capital,” we have incurred significant net losses since our inception and anticipate that we will continue to incur significant losses for the foreseeable future; and therefore, we do not know whether or when we will generate the U.S. federal or state taxable income necessary to utilize our NOLs or credits that are subject to limitation by Sections 382 and 383 of the Code.
For example: • others may be able to make products that are similar to our product candidates or utilize similar technology but that are not covered by the claims of the patents that we license or may own; • we, or our current or future licensors or collaborators, might not have been the first to make the inventions covered by the issued patent or pending patent application that we license or own now or in the future; • we, or our current or future licensors or collaborators, might not have been the first to file patent applications covering certain of our or their inventions; • others may independently develop similar or alternative technologies or duplicate any of our technologies without infringing our owned or licensed intellectual property rights; • it is possible that our current or future pending owned or licensed patent applications will not lead to issued patents; • issued patents that we hold rights to may be held invalid or unenforceable, including as a result of legal challenges by our competitors or other third parties; • our competitors or other third parties might conduct research and development activities in countries where we do not have patent rights and then use the information learned from such activities to develop competitive products for sale in our major commercial markets; • we may not develop additional proprietary technologies that are patentable; • the patents of others may harm our business; and 58 • we may choose not to file a patent in order to maintain certain trade secrets or know-how, and a third party may subsequently file a patent covering such intellectual property.
For example: • others may be able to make products that are similar to our product candidates or utilize similar technology but that are not covered by the claims of the patents that we license or may own; • we, or our current or future licensors or collaborators, might not have been the first to make the inventions covered by the issued patent or pending patent application that we license or own now or in the future; • we, or our current or future licensors or collaborators, might not have been the first to file patent applications covering certain of our or their inventions; • others may independently develop similar or alternative technologies or duplicate any of our technologies without infringing our owned or licensed intellectual property rights; 57 • it is possible that our current or future pending owned or licensed patent applications will not lead to issued patents; • issued patents that we hold rights to may be held invalid or unenforceable, including as a result of legal challenges by our competitors or other third parties; • our competitors or other third parties might conduct research and development activities in countries where we do not have patent rights and then use the information learned from such activities to develop competitive products for sale in our major commercial markets; • we may not develop additional proprietary technologies that are patentable; • the patents of others may harm our business; and • we may choose not to file a patent in order to maintain certain trade secrets or know-how, and a third party may subsequently file a patent covering such intellectual property.
Other potential consequences include, among other things: • restrictions on the marketing or manufacturing of our products, withdrawal of the product from the market or voluntary or mandatory product recalls; • fines, warning letters or holds on clinical trials; • refusal by the FDA to approve pending applications or supplements to approved applications filed by us or suspension or revocation of license approvals; • product seizure or detention or refusal to permit the import or export of our product candidates; and • injunctions or the imposition of civil or criminal penalties.
Other potential consequences include, among other things: • restrictions on the marketing or manufacturing of our products, withdrawal of the product from the market or voluntary or mandatory product recalls; 41 • fines, warning letters or holds on clinical trials; • refusal by the FDA to approve pending applications or supplements to approved applications filed by us or suspension or revocation of license approvals; • product seizure or detention or refusal to permit the import or export of our product candidates; and • injunctions or the imposition of civil or criminal penalties.
Failure to enter into and/or maintain additional significant licensing, distribution and/or collaboration agreements in a timely manner and on favorable terms to us may hinder or cause us to cease our efforts to develop and commercialize our product candidates, increase our development timelines, and/or increase our need to rely on partnering or financing mechanisms, such as sales of debt or equity securities, to fund our operations and continue our current and anticipated programs.
Failure to enter into and/or maintain significant licensing, distribution and/or collaboration agreements in a timely manner and on favorable terms to us may hinder or cause us to cease our efforts to develop and commercialize our product candidates, increase our development timelines, and/or increase our need to rely on partnering or financing mechanisms, such as sales of debt or equity securities, to fund our operations and continue our current and anticipated programs.
As another example, revisions to regulations under the federal anti-kickback statute would remove protection for traditional Medicare Part D discounts offered by pharmaceutical manufacturers to pharmacy benefit managers and health plans. Pursuant to court order, the removal was delayed and subsequent legislation imposed a moratorium on implementation of the rule until January 2032.
As another example, revisions to regulations under the federal anti-kickback statute would remove protection for traditional Medicare Part D discounts offered by pharmaceutical 42 manufacturers to pharmacy benefit managers and health plans. Pursuant to court order, the removal was delayed and subsequent legislation imposed a moratorium on implementation of the rule until January 2032.
We cannot guarantee that any of our or our licensors’ patent searches or analyses, including the identification of relevant patents, the scope of patent claims or the expiration of relevant patents, are complete or thorough, nor can we be certain that we have identified each and every third-party patent and pending patent application in the United States and abroad that is relevant to or necessary for the commercialization of our product candidates in any jurisdiction.
We cannot guarantee that any of our or our licensors’ patent searches or analyses, including the identification of relevant patents, the scope of patent claims or the expiration of relevant patents, are complete or thorough, nor can we be certain that we have 54 identified each and every third-party patent and pending patent application in the United States and abroad that is relevant to or necessary for the commercialization of our product candidates in any jurisdiction.
Failure to comply with these requirements could result in reputational risk, public reprimands, administrative penalties, fines or imprisonment. In addition, in most foreign countries, including the European Economic Area, the proposed pricing for a drug must be approved before it may be lawfully marketed. The requirements governing drug pricing and reimbursement vary widely from country to 44 country.
Failure to comply with these requirements could result in reputational risk, public reprimands, administrative penalties, fines or imprisonment. In addition, in most foreign countries, including the European Economic Area, the proposed pricing for a drug must be approved before it may be lawfully marketed. The requirements governing drug pricing and reimbursement vary widely from country to country.
We are subject to various domestic and international privacy and security regulations, including but not limited to the HIPAA, which mandates, among other things, the adoption of uniform standards for the electronic exchange of information in common healthcare transactions, as well as standards relating to the privacy and security of 60 individually identifiable health information, which require the adoption of administrative, physical and technical safeguards to protect such information.
We are subject to various domestic and international privacy and security regulations, including but not limited to the HIPAA, which mandates, among other things, the adoption of uniform standards for the electronic exchange of information in common healthcare transactions, as well as standards relating to the privacy and security of individually identifiable health information, which require the adoption of administrative, physical and technical safeguards to protect such information.
These anti-takeover provisions and other provisions in our certificate of incorporation and bylaws could make it more difficult for stockholders or potential acquirers to obtain control of our board of directors or initiate actions that are opposed by the then-current board of directors and could also delay or impede a merger, tender offer or proxy contest involving our company.
These anti-takeover provisions and other provisions in our certificate of incorporation and bylaws could make it more difficult for stockholders or potential acquirers to obtain control of our board of directors or initiate actions that are opposed by the then-current 63 board of directors and could also delay or impede a merger, tender offer or proxy contest involving our company.
There can be no assurance that we will be able to develop in-house sales and distribution capabilities or establish or maintain relationships with third-party collaborators to ensure compliance and support successful commercialization of any product in the United States or overseas. 31 Risks Related to Manufacturing and Supply Our product candidates are uniquely manufactured.
There can be no assurance that we will be able to develop in-house sales and distribution capabilities or establish or maintain relationships with third-party collaborators to ensure compliance and support successful commercialization of any product in the United States or overseas. Risks Related to Manufacturing and Supply Our product candidates are uniquely manufactured.
As a result, if we suffer losses due to our suppliers or manufacturers failure to perform, we will have limited remedies available against such suppliers and manufacturers and are unlikely to be able to recover such losses from them. 34 Third-party manufacturers may not be able to comply with cGMP regulations or similar regulatory requirements outside of the United States.
As a result, if we suffer losses due to our suppliers or manufacturers failure to perform, we will have limited remedies available against such suppliers and manufacturers and are unlikely to be able to recover such losses from them. Third-party manufacturers may not be able to comply with cGMP regulations or similar regulatory requirements outside of the United States.
These laws may impact, among other things, our current activities with principal investigators and research patients, as well as proposed and future sales, marketing and education programs. While we have adopted a corporate compliance program, we may not be able to protect against all potential issues of noncompliance.
These 46 laws may impact, among other things, our current activities with principal investigators and research patients, as well as proposed and future sales, marketing and education programs. While we have adopted a corporate compliance program, we may not be able to protect against all potential issues of noncompliance.
Our general business strategy may be adversely affected by any such economic downturn, volatile geopolitical and business environment or continued unpredictable and unstable market conditions. If the current equity and credit markets deteriorate, or do not improve, it may make any necessary debt or equity financing more difficult, more costly, and more dilutive.
Our general business strategy may be adversely affected by any such economic downturn, volatile geopolitical and business environment or continued unpredictable and unstable market conditions. If the current equity and credit markets deteriorate, or do not improve, it may make any necessary debt or equity financing more difficult, more costly, and 17 more dilutive.
Even though we have observed preliminary positive results based on an assessment of overall response rate and disease control rate to date in certain colorectal cancer settings, they may not necessarily be predictive of the final results of the trials or future clinical 19 trials or otherwise be sufficient to support an approval.
Even though we have observed preliminary positive results based on an assessment of overall response rate and disease control rate to date in certain colorectal cancer settings, they may not necessarily be predictive of the final results of the trials or future clinical trials or otherwise be sufficient to support an approval.
We engage third parties for clinical trials and/or to obtain necessary permits, licenses, patent registrations, and other regulatory approvals and we can be held liable for the corrupt or other illegal activities of our personnel, agents, or partners, even if we do not explicitly authorize or have prior knowledge of such activities.
We engage third parties for clinical trials and/or to obtain necessary permits, licenses, patent registrations, and other regulatory approvals and we can be held liable for the corrupt or other illegal activities of our personnel, agents, or partners, even if we do not explicitly authorize or have prior knowledge of such 45 activities.
Our issuance of additional preferred stock could make it more difficult for a third party to acquire a majority of our outstanding voting stock and thereby effect a change in the composition of our Board of Directors. Our certificate of incorporation also provides that our 64 stockholders may not take action by written consent.
Our issuance of additional preferred stock could make it more difficult for a third party to acquire a majority of our outstanding voting stock and thereby effect a change in the composition of our Board of Directors. Our certificate of incorporation also provides that our stockholders may not take action by written consent.
We may not be able to obtain or maintain orphan drug designations from the FDA for our current and future product candidates, as applicable. 39 Our strategy includes filing for orphan drug designation where available for our product candidates, but thus far, our applications for orphan drug designation with respect to balstilimab and zalifrelimab have been rejected.
We may not be able to obtain or maintain orphan drug designations from the FDA for our current and future product candidates, as applicable. Our strategy includes filing for orphan drug designation where available for our product candidates, but thus far, our applications for orphan drug designation with respect to balstilimab and zalifrelimab have been rejected.
The uncertainty resulting from the use of our product candidates in combination with other cancer therapies may make it difficult to accurately predict side effects in future clinical trials. The development of product candidates for use in combination with another product or product candidate may present challenges that are not faced for single agent product candidates.
The uncertainty resulting from the use of our product candidates in combination with other cancer therapies may make it difficult to accurately predict side effects in future clinical trials. 22 The development of product candidates for use in combination with another product or product candidate may present challenges that are not faced for single agent product candidates.
Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large, established companies. Established pharmaceutical companies may also invest heavily to accelerate discovery and 28 development of novel therapeutics or to in-license novel therapeutics that could make the product candidates that we develop obsolete.
Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large, established companies. Established pharmaceutical companies may also invest heavily to accelerate discovery and development of novel therapeutics or to in-license novel therapeutics that could make the product candidates that we develop obsolete.
For example, in February 2015, we began a broad collaboration with Incyte to pursue the discovery and development of antibodies, in December 2018 we entered into a partnership with Gilead relating to five of our antibody programs and in May 2021 we entered into a license agreement with BMS relating to our anti-TIGIT bispecific antibody program.
For example, in February 2015, we began a broad collaboration with Incyte to pursue the discovery and development of antibodies, in December 2018 we entered into a partnership with Gilead relating to five of our antibody programs and in May 2021 we entered into a license agreement with BMS relating to our anti-TIGIT bispecific antibody 34 program.
Additionally, since BMS, Incyte and Gilead, terminated their agreements with us, we may find it more difficult to attract new collaborators and our reputation in the business and financial communities could be adversely affected. Collaborations are complex and time-consuming to negotiate, document and execute.
Additionally, since BMS, Incyte and Gilead, terminated their agreements with us, we may find it more difficult to attract new collaborators and our reputation in the business and financial communities could be adversely affected. 35 Collaborations are complex and time-consuming to negotiate, document and execute.
The new regulatory requirements may impose 38 restrictions or post-approval commitments to monitor the safety and efficacy of our product candidates on an ongoing basis. In order for us to advance our product candidates, we will be required to consult with these regulatory agencies and comply with applicable requirements and guidelines.
The new regulatory requirements may impose restrictions or post-approval commitments to monitor the safety and efficacy of our product candidates on an ongoing basis. In order for us to advance our product candidates, we will be required to consult with these regulatory agencies and comply with applicable requirements and guidelines.
On the other hand, the allowance of narrower claims does not eliminate the potential for adversarial proceedings and may fail to provide a competitive advantage. Our issued patents may not contain claims sufficiently broad to protect us against third parties with similar technologies or products or provide us with any competitive advantage.
On the other hand, the allowance of narrower claims does not eliminate the potential 49 for adversarial proceedings and may fail to provide a competitive advantage. Our issued patents may not contain claims sufficiently broad to protect us against third parties with similar technologies or products or provide us with any competitive advantage.
In addition, court decisions may introduce uncertainty with respect to terms of a license agreement such as the impact of a challenge to the validity of a licensed patent on the payment obligations or termination rights of the license. We may not be able to protect our intellectual property rights throughout the world.
In addition, court decisions may introduce uncertainty with respect to terms of a 51 license agreement such as the impact of a challenge to the validity of a licensed patent on the payment obligations or termination rights of the license. We may not be able to protect our intellectual property rights throughout the world.
Obtaining and maintaining regulatory approval of our product candidates in one jurisdiction does not guarantee that we will be able to obtain or maintain regulatory approval in any other jurisdiction, while a failure or delay in obtaining regulatory approval in one jurisdiction may have a negative effect on the regulatory approval process in others.
Obtaining and maintaining regulatory approval of our product candidates in one jurisdiction does not guarantee that we will be able to obtain or maintain regulatory approval in any other jurisdiction, while a failure or delay in obtaining regulatory approval in one 26 jurisdiction may have a negative effect on the regulatory approval process in others.
We cannot be certain that, upon inspection, such regulatory authorities will determine that any of our clinical trials 37 comply with the GCP requirements. In addition, our clinical trials must be conducted with biologic product produced under cGMP requirements and may require a large number of patients.
We cannot be certain that, upon inspection, such regulatory authorities will determine that any of our clinical trials comply with the GCP requirements. In addition, our clinical trials must be conducted with biologic product produced under cGMP requirements and may require a large number of patients.
This process is expensive and time consuming, and we and our current or future licensors or licensees may not be able to file and prosecute all necessary or desirable patent applications at a reasonable cost or in a timely manner or in all jurisdictions where protection may be commercially advantageous.
This process is expensive and time consuming, and we and our current or future licensors or licensees may not be able to file and prosecute all necessary or desirable 48 patent applications at a reasonable cost or in a timely manner or in all jurisdictions where protection may be commercially advantageous.
Product liability claims may result in: • regulatory investigations; • injury to our reputation; • withdrawal of clinical trial volunteers; • costs of and distraction related to litigation; • substantial monetary awards to plaintiffs; and • decreased demand for any future products. We have limited product liability coverage for use of our product candidates.
Product liability claims may result in: • regulatory investigations; • injury to our reputation; • withdrawal of clinical trial volunteers; • costs of and distraction related to litigation; • substantial monetary awards to plaintiffs; and • decreased demand for any future products. 58 We have limited product liability coverage for use of our product candidates.
Furthermore, third parties, including regulatory authorities, may not accept or agree with our assumptions, estimates, calculations, conclusions or analyses or may interpret or weigh the importance of data differently, which could delay or prevent regulatory approval of, or limit commercial prospects for, the particular product candidate.
Furthermore, third parties, including regulatory authorities, may not accept or agree with our 21 assumptions, estimates, calculations, conclusions or analyses or may interpret or weigh the importance of data differently, which could delay or prevent regulatory approval of, or limit commercial prospects for, the particular product candidate.
In particular, the patent landscapes around the discovery, development, manufacture and commercial use of our product candidates are crowded. Third parties may have or obtain valid and enforceable patents or proprietary rights that could block us from developing product candidates using our technology.
In particular, the patent landscapes around the discovery, development, manufacture and commercial use of our product candidates are crowded. 53 Third parties may have or obtain valid and enforceable patents or proprietary rights that could block us from developing product candidates using our technology.
We may be subject to claims challenging the inventorship of our patents and other intellectual property. 57 We or our licensors may be subject to claims that former employees, collaborators or other third parties have an interest in our owned or in-licensed patent rights, trade secrets, or other intellectual property as an inventor or co-inventor.
We may be subject to claims challenging the inventorship of our patents and other intellectual property. We or our licensors may be subject to claims that former employees, collaborators or other third parties have an interest in our owned or in-licensed patent rights, trade secrets, or other intellectual property as an inventor or co-inventor.
The FCPA prohibits any U.S. individual or business from paying, 45 offering, authorizing payment or offering of anything of value, directly or indirectly, to any foreign official, political party or candidate for the purpose of influencing any act or decision of the foreign entity in order to assist the individual or business in obtaining or retaining business.
The FCPA prohibits any U.S. individual or business from paying, offering, authorizing payment or offering of anything of value, directly or indirectly, to any foreign official, political party or candidate for the purpose of influencing any act or decision of the foreign entity in order to assist the individual or business in obtaining or retaining business.
While we are not aware of any such material system failure, accident or security breach to date, if such an event were to occur and cause interruptions in our operations, it could result in a material disruption of our development programs and our business operations.
While we are not aware of any such material system failure, accident or security 59 breach to date, if such an event were to occur and cause interruptions in our operations, it could result in a material disruption of our development programs and our business operations.
The nature and length of our operating history may make it difficult to evaluate our technology and product development capabilities and predict our future performance. 17 We have no products approved for commercial sale and have not generated any revenue from product sales.
The nature and length of our operating history may make it difficult to evaluate our technology and product development capabilities and predict our future performance. We have no products approved for commercial sale and have not generated any revenue from commercial product sales.
Events that may prevent successful or timely completion of clinical development or prevent our ability to receive marketing approval for our product candidates include: • the FDA or comparable foreign regulatory authorities may require us to conduct additional preclinical studies or impose additional requirements before permitting us to initiate a clinical trial; • the FDA or comparable foreign regulatory authorities, Institutional Review Boards (“IRBs”) or ethics committees (“ECs”) may disagree with our study design, may require that we modify or amend our clinical trial protocols, or may not authorize us or our investigators to commence or conduct a clinical trial at a prospective trial site; • we may experience delays in reaching, or fail to reach, agreement on acceptable terms with trial sites and CROs, the terms of which can be subject to extensive negotiation and may vary significantly; • clinical investigators or clinical trial sites may deviate from trial protocols or GCP requirements or drop out of a trial, and we may need to add new investigators or sites; • our CROs may fail to comply with regulatory requirements or meet their contractual obligations to us in a timely manner, if at all; • the number of participants required for clinical trials may be larger than expected, enrollment in clinical trials may be slower than expected or participants may drop out or fail to return for post-treatment follow-up at a higher rate than expected; • the cost of clinical trials and preclinical studies may be greater than we anticipate, or we may have insufficient funds to conduct such trial or study or to pay the substantial user fees required by the FDA upon the submission of a BLA; • the supply or quality of our product candidates or other materials necessary to conduct our clinical trials or preclinical studies may be insufficient or inadequate to initiate or complete a given clinical trial; • our product candidates may have undesirable side effects or other unexpected characteristics that are viewed to outweigh their potential benefits; • reports from clinical testing of other similar therapies may raise safety, tolerability or efficacy concerns about our product candidates; and • clinical trials of our product candidates may fail to show appropriate safety, purity or potency of our product candidates, may produce negative or inconclusive results or may otherwise fail to improve on the existing standard of care, and we may 20 decide, or regulators may require us, to conduct additional clinical trials or preclinical studies or we may decide to abandon product candidate development.
Events that may prevent successful or timely completion of clinical development or prevent our ability to receive marketing approval for our product candidates include: • the FDA or comparable foreign regulatory authorities may require us to conduct additional preclinical studies or impose additional requirements before permitting us to initiate a clinical trial; • the FDA or comparable foreign regulatory authorities, Institutional Review Boards (“IRBs”) or ethics committees (“ECs”) may disagree with our study design, may require that we modify or amend our clinical trial protocols, or may not authorize us or our investigators to commence or conduct a clinical trial at a prospective trial site; 19 • we may experience delays in reaching, or fail to reach, agreement on acceptable terms with trial sites and Clinical Research Organizations ("CRO"), the terms of which can be subject to extensive negotiation and may vary significantly; • clinical investigators or clinical trial sites may deviate from trial protocols or GCP requirements or drop out of a trial, and we may need to add new investigators or sites; • our CROs may fail to comply with regulatory requirements or meet their contractual obligations to us in a timely manner, if at all; • the number of participants required for clinical trials may be larger than expected, enrollment in clinical trials may be slower than expected or participants may drop out or fail to return for post-treatment follow-up at a higher rate than expected; • the cost of clinical trials and preclinical studies may be greater than we anticipate, or we may have insufficient funds to conduct such trial or study or to pay the substantial user fees required by the FDA upon the submission of a BLA; • the supply or quality of our product candidates or other materials necessary to conduct our clinical trials or preclinical studies may be insufficient or inadequate to initiate or complete a given clinical trial; • our product candidates may have undesirable side effects or other unexpected characteristics that are viewed to outweigh their potential benefits; • reports from clinical testing of other similar therapies may raise safety, tolerability or efficacy concerns about our product candidates; and • clinical trials of our product candidates may fail to show appropriate safety, purity or potency of our product candidates, may produce negative or inconclusive results or may otherwise fail to improve on the existing standard of care, and we may decide, or regulators may require us, to conduct additional clinical trials or preclinical studies or we may decide to abandon product candidate development.
In addition, the rights granted under any issued patents may not provide us with protection or competitive advantages against competitors with similar technology. Furthermore, our competitors may independently develop similar technologies. For these reasons, we may have competition for our product candidates.
In addition, the rights granted under any issued patents may not provide us with protection or competitive advantages against competitors with similar 50 technology. Furthermore, our competitors may independently develop similar technologies. For these reasons, we may have competition for our product candidates.
These products may compete with our product candidates, and our patents or other intellectual property rights may not be effective or sufficient to prevent them from competing. 52 Many companies have encountered significant problems in protecting and defending intellectual property rights in foreign jurisdictions.
These products may compete with our product candidates, and our patents or other intellectual property rights may not be effective or sufficient to prevent them from competing. Many companies have encountered significant problems in protecting and defending intellectual property rights in foreign jurisdictions.
Our determination of the expiration date of any patent in the United States or abroad that we consider relevant may be incorrect, which may negatively impact our ability to develop and market our 55 product candidates. Our failure to identify and correctly interpret relevant patents may negatively impact our ability to develop and market our product candidates.
Our determination of the expiration date of any patent in the United States or abroad that we consider relevant may be incorrect, which may negatively impact our ability to develop and market our product candidates. Our failure to identify and correctly interpret relevant patents may negatively impact our ability to develop and market our product candidates.
No assurance is given that our procedures and processes for detecting weaknesses in our internal control over financial reporting will be effective. Changing laws, regulations and standards relating to corporate governance and public disclosure, are creating uncertainty for companies.
No assurance is given that our procedures and processes for detecting weaknesses in our internal control over financial reporting will be effective. 62 Changing laws, regulations and standards relating to corporate governance and public disclosure, are creating uncertainty for companies.
In such an event, our trials could be suspended or terminated, and the FDA or comparable foreign regulatory authorities could order us to cease further development of or deny approval of our product 27 candidates for any or all targeted indications.
In such an event, our trials could be suspended or terminated, and the FDA or comparable foreign regulatory authorities could order us to cease further development of or deny approval of our product candidates for any or all targeted indications.
Consequently, the level of protection, if any, that will be provided by our patents if we attempt to enforce them and they are challenged, is uncertain. In addition, the type and extent of patent claims that will be issued to us in the future is 50 uncertain.
Consequently, the level of protection, if any, that will be provided by our patents if we attempt to enforce them and they are challenged, is uncertain. In addition, the type and extent of patent claims that will be issued to us in the future is uncertain.
In addition, we have limited internal resources and if we fail to recruit and/or retain the services of key employees and external consultants as needed, we may not be able to achieve our strategic and operational objectives. 59 Garo H.
In addition, we have limited internal resources and if we fail to recruit and/or retain the services of key employees and external consultants as needed, we may not be able to achieve our strategic and operational objectives. Garo H.
In addition, clinical trial delays could shorten any periods during which we may have the exclusive right to commercialize our product candidates or allow our competitors to bring products to market before we do, which could impair our ability to successfully commercialize our product candidates.
In addition, clinical trial delays could shorten any 20 periods during which we may have the exclusive right to commercialize our product candidates or allow our competitors to bring products to market before we do, which could impair our ability to successfully commercialize our product candidates.
We may seek to utilize, among other strategies, FDA’s accelerated approval program for our product candidates given the limited alternatives for treatments for certain rare diseases, cancer and autoimmune diseases, but the FDA may not agree with our plans.
We may seek to utilize, among other strategies, FDA’s accelerated approval program for our product candidates given the limited alternatives for treatments for certain rare diseases, cancer and autoimmune diseases, but the FDA may 25 not agree with our plans.
Even if we receive accelerated approval from the FDA for one or more of our product candidates, 26 there is no guarantee that we will be able to successfully complete one or more confirmatory trials needed to obtain full approval.
Even if we receive accelerated approval from the FDA for one or more of our product candidates, there is no guarantee that we will be able to successfully complete one or more confirmatory trials needed to obtain full approval.
Drug pricing and payment reform was 43 a focus of the prior Trump administration and that focus is likely to continue under the current administration. Other potential healthcare reform efforts under the current administration may affect access to healthcare coverage or the funding of health care benefits.
Drug pricing and payment reform was a focus of the prior Trump administration and that focus is likely to continue under the current administration. Other potential healthcare reform efforts under the current administration may affect access to healthcare coverage or the funding of health care benefits.
Third parties may have blocking patents that could prevent us from marketing our own patented 49 product and practicing our own patented technology. Any of these outcomes could impair our ability to prevent competition from third parties, which may have an adverse impact on our business.
Third parties may have blocking patents that could prevent us from marketing our own patented product and practicing our own patented technology. Any of these outcomes could impair our ability to prevent competition from third parties, which may have an adverse impact on our business.
The ultimate success of these strategic transactions entails numerous operational and financial risks, including: 61 • higher than expected development and integration costs; • difficulty in combining the technologies, operations and personnel of acquired businesses with our technologies, operations and personnel; • exposure to unknown liabilities; • difficulty or inability to form a unified corporate culture across multiple office sites both nationally and internationally; • inability to retain key employees of acquired businesses; • disruption of our business and diversion of our management’s time and attention; and • difficulty or inability to secure financing to fund development activities for such acquired or in-licensed product candidates, technologies or businesses.
The ultimate success of these strategic transactions entails numerous operational and financial risks, including: 60 • higher than expected development and integration costs; • difficulty in combining the technologies, operations and personnel of acquired businesses with our technologies, operations and personnel; • exposure to unknown liabilities; • difficulty or inability to form a unified corporate culture across multiple office sites both nationally and internationally; • inability to retain key employees of acquired businesses; • disruption of our business and diversion of our management’s time and attention; and • difficulty or inability to secure financing to fund development activities for such acquired or in-licensed product candidates, technologies or businesses.
We will require additional capital to fund our operations, and if we fail to obtain necessary financing, we will not be able to complete the development and commercialization of our product candidates. Our operations have consumed substantial amounts of cash since inception.
We will require additional capital to fund our operations, and if we fail to obtain necessary financing, we will not be able to complete the development and commercialization of our product candidates. 15 Our operations have consumed substantial amounts of cash since inception.
The FDA and comparable authorities in other countries have substantial discretion in the approval process and may refuse to accept any application or may decide that our data are insufficient for approval and require additional preclinical, clinical or other studies.
The FDA and comparable authorities in other countries have substantial discretion in the approval process and may refuse to accept any application or may decide that our data are insufficient for approval and require 24 additional preclinical, clinical or other studies.
These third parties may also have relationships with other commercial entities, including our competitors, for whom they may also be conducting clinical trials or other product development activities, which could affect their performance on our behalf.
These third parties may also have relationships with other commercial 36 entities, including our competitors, for whom they may also be conducting clinical trials or other product development activities, which could affect their performance on our behalf.
To the extent that an individual who is not obligated to assign 53 rights in intellectual property to us is rightfully an inventor of intellectual property, we may need to obtain an assignment or a license to that intellectual property from that individual, or a third party or from that individual’s assignee.
To the extent that an individual who is not obligated to assign rights in intellectual property to us is rightfully an inventor of intellectual property, we may need to obtain an assignment or a license to that intellectual property from that individual, or a third party or from that individual’s assignee.
If external funding is available, there is no guarantee that it will be on attractive or acceptable terms, or that it will be adequate to advance the business to an inflection point for additional funding. Similarly, there is no guarantee that partnership opportunities will be available on attractive terms, if at all.
If funding is available, there is no guarantee that it will be on attractive or acceptable terms, or that it will be adequate to advance the business to an inflection point for additional funding. Similarly, there is no guarantee that partnership opportunities will be available on attractive terms, if at all.
These setbacks have been caused by, among other things, preclinical and other nonclinical findings made while clinical trials were underway, or safety or efficacy observations made in preclinical studies and clinical trials, including previously unreported 23 adverse events.
These setbacks have been caused by, among other things, preclinical and other nonclinical findings made while clinical trials were underway, or safety or efficacy observations made in preclinical studies and clinical trials, including previously unreported adverse events.
Even if we obtain significant market share for our product candidates, because certain of the potential target populations are small, we may never achieve profitability without obtaining regulatory approval for additional indications.
Even if we obtain significant market share for 30 our product candidates, because certain of the potential target populations are small, we may never achieve profitability without obtaining regulatory approval for additional indications.
Additionally, over the last 46 several years , the U.S. government has shut down several times and certain regulatory agencies, such as the FDA, have had to furlough critical FDA and other government employees and stop critical activities.
Additionally, over the last several years , the U.S. government has shut down several times and certain regulatory agencies, such as the FDA, have had to furlough critical FDA and other government employees and stop critical activities.
If we are able to find a replacement supplier, the replacement 33 supplier would need to be qualified and may require additional regulatory authority approval, which could result in further delay and additional costs.
If we are able to find a replacement supplier, the replacement supplier would need to be qualified and may require additional regulatory authority approval, which could result in further delay and additional costs.
Publication of discounts by third-party payors or authorities may lead to further pressure on the prices or reimbursement levels within the country of publication and other countries.
Publication of discounts by third-party payors 43 or authorities may lead to further pressure on the prices or reimbursement levels within the country of publication and other countries.
While we are not aware of any downgrades, material losses, or other significant deterioration in the fair value of our cash equivalents and investments since December 31, 2024, no assurance can be given that deterioration of the global credit and financial markets would not negatively impact our current portfolio of cash equivalents or our ability to meet our financing objectives.
While we are not aware of any downgrades, material losses, or other significant deterioration in the fair value of our cash equivalents and investments since December 31, 2025, no assurance can be given that deterioration of the global credit and financial markets would not negatively impact our current portfolio of cash equivalents or our ability to meet our financing objectives.
Our manufacturing process may be susceptible to logistical issues associated with the collection of materials sourced from various suppliers as well as shipment of the final product to clinical centers, manufacturing issues associated with interruptions in the manufacturing process, contamination, equipment or reagent failure, improper installation or operation of equipment, vendor or operator error, inconsistency in production batches, and variability in product characteristics.
Our manufacturing process may be susceptible to logistical issues associated with the CMO relationship, the collection of materials sourced from various suppliers as well as shipment of the final product to clinical centers, manufacturing issues associated with interruptions in the manufacturing process, contamination, equipment or reagent failure, improper installation or operation of equipment, vendor or operator error, inconsistency in production batches, and variability in product characteristics.
Our future success depends on our ability to manufacture our products on a timely basis with acceptable manufacturing costs, while at the same time maintaining good quality control and complying with applicable regulatory requirements, and an inability to do so could have a material adverse effect on our business, financial condition, and results of operations.
Our future success depends on our ability to have our products manufactured on a timely basis with acceptable manufacturing costs, while at the same time maintaining good quality control and complying with applicable regulatory requirements, and an inability to do so could have a material adverse effect on our business, financial condition, and results of operations.
Risks Related to Our Reliance on Third Parties We are dependent upon our collaboration with Betta to further develop and commercialize certain antibody programs.
Risks Related to Our Reliance on Third Parties We are dependent upon our collaboration with third parties to further develop and commercialize certain antibody programs.
As a result of the UK exiting the EU, commonly known as Brexit, since January 1, 2021, any transfers of personal data to the UK are subject to the requirements of Chapter V of the GDPR and of the Law Enforcement Directive and absent an adequacy finding under GDPR, transfers of personal data from the EU to the UK, including to our facility in Cambridge, UK, would be illegal without adequate safeguards provided for under EC-approved mechanisms, such as current standard contractual clauses or, if approved in the future, an EU-UK privacy shield similar to the current framework in place between the EU and the United States.
As a result of the UK exiting the EU, commonly known as Brexit, since January 1, 2021, any transfers of personal data to the UK are subject to the requirements of Chapter V of the GDPR and of the Law Enforcement Directive and absent an adequacy finding under GDPR, transfers of personal data from the EU to the UK, would be illegal without adequate safeguards provided for under EC-approved mechanisms, such as current standard contractual clauses or, if approved in the future, an EU-UK privacy shield similar to the current framework in place between the EU and the United States.
Global credit and financial markets have experienced extreme volatility and disruptions in the past several years, including increased inflation, severely diminished liquidity and credit availability, declines in consumer confidence, declines in economic growth, increases in unemployment rates and uncertainty about economic stability, and the volatility of such market and economic conditions have increased as a result of the conflicts in the Middle East and the Russian invasion of Ukraine, and may increase as a result of other geopolitical actions, including newly imposed tariffs and other actions that directly or indirectly impact the global economy.
Global credit and financial markets have experienced extreme volatility and disruptions in the past several years, including increased inflation, severely diminished liquidity and credit availability, declines in consumer confidence, declines in economic growth, increases in unemployment rates and uncertainty about economic stability, and the volatility of such market and economic conditions have increased as a result of the conflicts in the Middle East and the Russian invasion of Ukraine, and may increase as a result of other geopolitical actions, including new or ongoing tariffs and other actions that directly or indirectly impact the global economy.
While our management has concluded that there were no material weaknesses in our internal control over financial reporting as of December 31, 2024, our procedures are subject to the risk that our controls may become inadequate because of changes in conditions or as a result of a deterioration in compliance with such 63 procedures.
While our management has concluded that there were no material weaknesses in our internal control over financial reporting as of December 31, 2025, our procedures are subject to the risk that our controls may become inadequate because of changes in conditions or as a result of a deterioration in compliance with such procedures.

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Item 1C. Cybersecurity

Cybersecurity — threats and controls disclosure

1 edited+0 added−0 removed7 unchanged
Biggest changeOur cybersecurity team monitors the prevention and detection of cybersecurity events and is responsible for incident response and remediation.
Biggest changeOur cybersecurity team monitors the prevention and detection of cybersecurity events and is responsible for incident response and remediation. 64

Item 2. Properties

Properties — owned and leased real estate

1 edited+0 added−2 removed1 unchanged
Biggest changeItem 2. Pr operties We lease our main research and development, manufacturing and corporate offices in Lexington, Massachusetts occupying approximately 82,000 square feet. This lease agreement terminates in August 2033. We own a manufacturing facility of approximately 24,000 square feet in Berkeley, California that is used in the production and manufacture of antibody product candidates.
Biggest changeItem 2. Pr operties We lease our main research and development, manufacturing and corporate offices in Lexington, Massachusetts occupying approximately 82,000 square feet. This lease agreement terminates in August 2033. We believe substantially all of our property and equipment is in good condition and that we have sufficient capacity to meet our current operational needs.
Removed
In November 2020, we entered into a long-term lease in Emeryville, California for cGMP commercial manufacturing space. Construction of this end-to-end 83,000 square foot clinical and commercial biologics manufacturing facility (from cell line development through Drug Product fill & finish, packaging and labeling) has been completed and the facility is being commissioned for GMP manufacturing.
Removed
This lease terminates in December 2036 with the option to renew for two additional ten-year terms. We also lease research and office facilities in Cambridge, United Kingdom. This lease terminates in November 2025. We believe substantially all of our property and equipment is in good condition and that we have sufficient capacity to meet our current operational needs.

Item 3. Legal Proceedings

Legal Proceedings — active lawsuits and investigations

5 edited+4 added−3 removed2 unchanged
Biggest changeWe have produced records pursuant to the subpoena. At this time, the Company cannot predict the outcome of the SEC’s investigation. We are not currently a party to any other material legal proceedings. From time to time, we may be subject to various legal proceedings and claims that arise in the ordinary course of our business activities.
Biggest changeSecurities and Exchange Commission (the “SEC”) seeking records relating to certain of our product candidates, correspondence with the FDA, public disclosure, and other matters. We have produced records pursuant to the subpoena. At this time, the Company cannot predict the outcome of the SEC’s investigation. We are not currently a party to any other material legal proceedings.
The lawsuit alleges that the defendants violated Sections 10(b) and 20(a) of the Securities Exchange Act of 1934, as amended, and Rule 10b-5 thereunder, by making false and misleading statements and omissions of material fact related to the efficacy and commercial prospects of botensilimab and balstilimab.
The amended complaint alleges that Agenus, three of its current officers, and one member of its advisory board violated Sections 10(b) and 20(a) of the Securities Exchange Act of 1934, as amended, and Rule 10b-5 thereunder, by making false and misleading statements and omissions of material fact related to the efficacy and commercial prospects of botensilimab and balstilimab.
The lead plaintiff seeks to represent all persons who purchased or otherwise 66 acquired Agenus securities between January 23, 2023, and July 17, 2024 and seeks damages and interest, and an award of costs, including attorneys’ fees. We have not recorded any accrual for a contingent liability associated with these legal proceedings.
The lead plaintiff seeks to represent all persons who purchased or otherwise acquired Agenus securities between January 23, 2023, and July 17, 2024, and seeks damages and interest, and an award of costs, including attorneys’ fees. On April 8, 2025, the Company moved to dismiss the securities class action.
Armen, et al. , No. 1:24-cv-13083 (the “Ferraioli Action”). The actions name certain of the Company’s executives and directors and allege that defendants made false or misleading statements and omissions of material fact related to the efficacy and commercial prospects of botensilimab and balstilimab.
The actions name certain of the Company’s executives and directors and allege that defendants made false or misleading statements and omissions of material fact related to the efficacy and commercial prospects of botensilimab and balstilimab. Plaintiffs seek an award of damages and an order directing the Company to reform and improve its corporate governance and internal procedures.
Regardless of the outcome, litigation can have a material adverse effect on us because of defense and settlement costs, diversion of management resources and other factors. Item 4. Mine Saf ety Disclosures Not applicable. 67 PART II
From time to time, we may be subject to various legal proceedings and claims that arise in the ordinary course of our business activities. Regardless of the outcome, litigation can have a material adverse effect on us because of defense and settlement costs, diversion of management resources and other factors. Item 4.
Removed
The defendants’ deadline to respond to the complaint is April 8, 2025. The Company has been served with three derivative actions in the Court filed by purported stockholders, captioned Royse v. Armen, et al. , No. 1:24-cv-12823 (the “Royse Action”); Chen v. Armen, et al. , No. 1:24-cv-13088 (the “Chen Action”), Ferraioli v.
Added
On June 6, 2025 plaintiff filed an opposition to the motion to dismiss, and on July 7, 2025, the Company filed its reply brief. Oral argument on the motion to dismiss was held on March 3, 2026. As of the date of this filing, the Company’s motion to dismiss is pending before the court.
Removed
Plaintiffs seek an award of damages and an order directing the Company to reform and improve its corporate governance and internal procedures. The Court consolidated the Royse Action and Chen Action on January 16, 2025 and defendants submitted an unopposed motion to stay all deadlines pending future developments in the securities class action on February 25, 2025.
Added
We have not recorded any accrual for a contingent liability associated with these legal proceedings. The Company has been served with four derivative actions filed in the Court between November 2024 and January 2025 by purported stockholders.
Removed
Defendants’ deadline to respond to the complaint in the Ferraioli Action is March 10, 2025. In September 2024, the Company received a subpoena from the Boston Regional Office of the U.S. Securities and Exchange Commission (the “SEC”) seeking records relating to certain of our product candidates, correspondence with the FDA, public disclosure, and other matters.
Added
On May 2, 2025, the Court consolidated the four actions in Case No. 1:24-cv-12823 and stayed all deadlines pending future developments in the securities class action. In September 2024, the Company received a subpoena from the Boston Regional Office of the U.S.
Added
Mine Saf ety Disclosures Not applicable. 65 PART II

Item 5. Market for Registrant's Common Equity

Market for Common Equity — stock, dividends, buybacks

3 edited+1 added−1 removed5 unchanged
Biggest changeCOMPANIES) INDEX AND NASDAQ BIOTECHNOLOGY INDEX 68 12/31/2019 12/31/2020 12/31/2021 12/31/2022 12/31/2023 12/31/2024 Agenus Inc. $ 100.00 $ 78.13 $ 79.12 $ 58.97 $ 20.39 $ 3.37 Nasdaq Stock Market (U.S.
Biggest changeCOMPANIES) INDEX AND NASDAQ BIOTECHNOLOGY INDEX 66 12/31/2020 12/31/2021 12/31/2022 12/31/2023 12/31/2024 12/31/2025 Agenus Inc. $ 100.00 $ 101.26 $ 75.47 $ 26.10 $ 4.31 $ 4.94 Nasdaq Stock Market (U.S.
Stock Performance The following graph shows the cumulative total stockholder return on our common stock over the period spanning December 31, 2019 to December 31, 2024, as compared with that of the Nasdaq Stock Market (U.S. Companies) Index and the Nasdaq Biotechnology Index, based on an initial investment of $100 in each on December 31, 2019.
Stock Performance The following graph shows the cumulative total stockholder return on our common stock over the period spanning December 31, 2020 to December 31, 2025, as compared with that of the Nasdaq Stock Market (U.S. Companies) Index and the Nasdaq Biotechnology Index, based on an initial investment of $100 in each on December 31, 2020.
Item 5. Market for Registrant’s Common Equity, Related Sto ckholder Matters and Issuer Purchases of Equity Securities Our common stock is currently listed on The Nasdaq Capital Market under the symbol “AGEN.” As of February 28, 2025, there were 360 holders of record of our common stock.
Item 5. Market for Registrant’s Common Equity, Related Sto ckholder Matters and Issuer Purchases of Equity Securities Our common stock is currently listed on The Nasdaq Capital Market under the symbol “AGEN.” As of February 28, 2026, there were 178 holders of record of our common stock.
Removed
Companies) Index $ 100.00 $ 143.64 $ 174.36 $ 116.65 $ 167.30 $ 215.22 Nasdaq Biotechnology Index $ 100.00 $ 125.69 $ 124.89 $ 111.27 $ 115.42 $ 113.84 Item 6. [Reserved] 69
Added
Companies) Index $ 100.00 $ 121.39 $ 81.21 $ 116.47 $ 149.83 $ 180.33 Nasdaq Biotechnology Index $ 100.00 $ 99.37 $ 88.53 $ 91.84 $ 90.58 $ 119.92 Item 6. [Reserved] 67

Item 7. Management's Discussion & Analysis

Management's Discussion & Analysis (MD&A) — revenue / margin commentary

45 edited+16 added−20 removed47 unchanged
Biggest changeNon-operating income Non-operating income increased $5.8 million for the year ended December 31, 2024, from income of $37,000 for the year ended December 31, 2023, to income of $5.8 million for the year ended December 31, 2024, primarily due to the recognition of a $5.3 million gain on the early termination of two operating leases and the recognition of R&D tax credits in the UK, compared to de minimis activity in 2023.
Biggest changeNon-operating income (expense) Non-operating expense increased $8.1 million for the year ended December 31, 2025, from income of $5.8 million for the year ended December 31, 2024, to expense of $2.2 million for the year ended December 31, 2025, primarily due to the $3.5 million loss on the deconsolidation of a certain foreign subsidiary, partially offset by the recognition of R&D tax credits in the UK in 2025, compared to the recognition of a $5.3 million gain on the early termination of two operating leases and the recognition of R&D tax credits in the UK in 2024.
Such factors include, but are not limited to, failures or delays in clinical development, failure to receive marketing approval from governmental health authorities or delay in that approval, changing standards of care, the introduction of competing products, manufacturing or other delays, biosimilar competition, patent protection, adverse events that result in governmental health authority imposed restrictions on the use of the drug products, significant changes in foreign exchange rates, and other events or circumstances that could result in reduced royalty payments made to the purchasers, all of which would result in a reduction of non-cash royalty revenues and the non-cash interest expense over the life of the associated agreement.
Such factors include, but are not limited to, failures or delays in clinical development, failure to receive marketing approval from governmental health authorities or delay in that approval, changing standards of care, the introduction of competing products, manufacturing or other delays, biosimilar competition, patent protection, adverse events that result in governmental health authority imposed restrictions on the use of the drug products, significant changes in foreign exchange rates, and other events or circumstances that could result in reduced royalty payments made to the purchasers, all of which would result in a 74 reduction of non-cash royalty revenues and the non-cash interest expense over the life of the associated agreement.
These studies have been carried out by academic institutions and pharmaceutical companies in the United 74 States and internationally. A number of these studies have shown QS-21 to be significantly more effective in stimulating immune responses than aluminum hydroxide or aluminum phosphate, the adjuvants most commonly used in approved vaccines in the United States today.
These studies have been carried out by academic institutions and pharmaceutical companies in the United States and internationally. A number of these studies have shown QS-21 to be significantly more effective in stimulating immune responses than aluminum hydroxide or aluminum phosphate, the adjuvants most commonly used in approved vaccines in the United States today.
The timing of expense recognition and future payments related to these agreements is subject to the enrollment of patients and performance by the applicable third-party provider. We plan to enter into additional agreements with third party providers and we anticipate significant additional expenditures will be required to initiate and advance our various programs.
The timing of expense recognition and future payments related to these agreements is subject to the 73 enrollment of patients and performance by the applicable third-party provider. We plan to enter into additional agreements with third party providers and we anticipate significant additional expenditures will be required to initiate and advance our various programs.
We have recorded the proceeds from these transactions as a liability on our consolidated balance sheets that will be amortized using the interest method over the estimated life of the associated agreement. 76 As a result, we impute interest on the transactions and record non-cash interest expense at the estimated interest rate.
We have recorded the proceeds from these transactions as a liability on our consolidated balance sheets that will be amortized using the interest method over the estimated life of the associated agreement. As a result, we impute interest on the transactions and record non-cash interest expense at the estimated interest rate.
In 2024, Merck notified us that the further clinical development of MK-4830 will be limited to a 70 neoadjuvant ovarian study of MK-4830 in combination with pembrolizumab and chemotherapy with or without bevacizumab that is ongoing.
In 2024 Merck notified us that the further clinical development of MK-4830 will be limited to a neoadjuvant ovarian study of MK-4830 in combination with pembrolizumab and chemotherapy with or without bevacizumab that is ongoing.
In January 2018, we entered into a Royalty Purchase Agreement with Healthcare Royalty Partners III, L.P. and certain of its affiliates (together, “HCR”), pursuant to which HCR 71 purchased 100% of our worldwide rights to receive royalties from GSK on GSK’s sales of vaccines containing our QS-21 adjuvant. We do not incur clinical development costs for products partnered with GSK.
In January 2018, we entered into a Royalty Purchase 69 Agreement with Healthcare Royalty Partners III, L.P. and certain of its affiliates (together, “HCR”), pursuant to which HCR purchased 100% of our worldwide rights to receive royalties from GSK on GSK’s sales of vaccines containing our QS-21 adjuvant. We do not incur clinical development costs for products partnered with GSK.
Please see the “Note Regarding Forward-Looking Statements” of this Annual Report on Form 10-K and the risks highlighted under Part I-Item 1A. “Risk Factors” of this Annual Report on Form 10-K. The table below summarizes our material cash requirements from known contractual and other obligations as of December 31, 2024 (in thousands).
Please see the “Note Regarding Forward-Looking Statements” of this Annual Report on Form 10-K and the risks highlighted under Part I-Item 1A. “Risk Factors” of this Annual Report on Form 10-K. The table below summarizes our material cash requirements from known contractual and other obligations as of December 31, 2025 (in thousands).
We are likely to continue to incur losses until we become a commercial company generating profits. Historical Results of Operations The comparison of 2023 to 2022 results has been omitted from this Form 10-K but can be found in our Form 10-K for the year ended December 31, 2023 – “Item 7.
We are likely to continue to incur losses until we become a commercial company generating profits. Historical Results of Operations The comparison of 2024 to 2023 results has been omitted from this Form 10-K but can be found in our Form 10-K for the year ended December 31, 2024 – “Item 7.
As described in Note 17 to our Consolidated Financial Statements, this transaction has been recorded as a liability that amortizes over the estimated life of our Royalty Purchase Agreement with HCR. As a result of this liability accounting, even though the royalties are remitted directly to HCR, we record these royalties from GSK as revenue.
As described in Note 18 to our Consolidated Financial Statements, this transaction has been recorded as a liability that amortizes over the estimated life of our Royalty Purchase Agreement with HCR. As a result of this liability accounting, even though the royalties are remitted directly to HCR, we record these royalties from GSK as revenue.
Cell Therapies Our majority owned subsidiary, MiNK, is a focused on developing allogeneic iNKT cell therapies to treat cancer and other immune-mediated diseases. iNKTs have a dual-mechanism of action with an internal targeting and homing device that modulates both arms of immunity, innate and adaptive. iNKTs combine the killing features of natural killer cells with the durable memory response of T cells. iNKT cells have been demonstrated to be highly effective in treating solid tumor cancers in their native form and MiNK has demonstrated that these cells can be further engineered or edited for super-targeting.
MiNK, is a focused on developing allogeneic iNKT cell therapies to treat cancer and other immune-mediated diseases. iNKTs have a dual-mechanism of action with an internal targeting and homing device that modulates both arms of immunity, innate and adaptive. iNKTs combine the killing features of natural killer cells with the durable memory response of T cells. iNKT cells have been demonstrated to be highly effective in treating solid tumor cancers in their native form and MiNK has demonstrated that these cells can be further engineered or edited for super-targeting.
Our I-O portfolio is driven by several platforms and programs, which we plan to utilize individually and in combination: • Multiple antibody discovery platforms, including proprietary display technologies, to identify future antibody candidates. • Antibody candidate programs, including our lead assets, botensilimab ("BOT") (a multifunctional immune cell activator and human Fc-enhanced cytotoxic T-lymphocyte antigen 4 (CTLA-4) blocking antibody, also known as AGEN1181) and balstilimab ("BAL") (a programmed death receptor-1 (PD-1) blocking antibody). • Our saponin-based vaccine adjuvant platform, primarily centered around our STIMULON™ cultured plant cell (“cpc”) QS-21 adjuvant (“STIMULON cpcQS-21”). • A pipeline of novel allogeneic invariant natural killer T cell (“iNKT”) therapies for treating cancer and other immune-mediated diseases, controlled by MiNK.
Our I-O portfolio is driven by several platforms and programs, which we plan to utilize individually and in combination: • Multiple antibody discovery platforms, including proprietary display technologies, to identify future antibody candidates. • Antibody candidate programs, including our lead assets, botensilimab ("BOT") (a multifunctional immune cell activator and human Fc-enhanced CTLA-4 blocking antibody, also known as AGEN1181) and balstilimab ("BAL") (a PD-1 blocking antibody). • Our saponin-based vaccine adjuvant platform, primarily centered around our STIMULON™ cultured plant cell (“cpc”) QS-21 adjuvant (“STIMULON cpcQS-21”). • A pipeline of novel allogeneic invariant natural killer T cell (“iNKT”) therapies for treating cancer and other immune-mediated diseases, controlled by MiNK.
Inflation We believe that inflation has not had a material adverse effect on our business, results of operations, or financial condition to date. 73 Research and Development Programs For the year ended December 31, 2024, our R&D programs consisted largely of our antibody programs as indicated in the following table (in thousands).
Inflation We believe that inflation has not had a material adverse effect on our business, results of operations, or financial condition to date. Research and Development Programs For the year ended December 31, 2025, our R&D programs consisted largely of our antibody programs as indicated in the following table (in thousands).
For additional information regarding iNKT cell therapies, please read Part I-Item 1. “Business” of this Annual Report on Form 10-K. Liquidity and Capital Resources We have incurred annual operating losses since inception, and we had an accumulated deficit of $2.18 billion as of December 31, 2024.
For additional information regarding iNKT cell therapies, please read Part I-Item 1. “Business” of this Annual Report on Form 10-K. 72 Liquidity and Capital Resources We have incurred annual operating losses since inception, and we had an accumulated deficit of $2.18 billion as of December 31, 2025.
Recent Accounting Pronouncements Refer to Note 2 to our consolidated financial statements included within Item 8 of this Annual Report on Form 10-K for a description of recent accounting pronouncements applicable to our business. 77
Recent Accounting Pronouncements Refer to Note 2 to our consolidated financial statements included within Item 8 of this Annual Report on Form 10-K for a description of recent accounting pronouncements applicable to our business. 75
Net cash used in operating activities for the years ended December 31, 2024 and 2023 was $158.3 million and $224.2 million, respectively. Our future ability to generate cash from operations will depend on achieving regulatory approval and market acceptance of our product candidates, achieving benchmarks as defined in existing collaboration agreements, and our ability to enter into new collaborations.
Net cash used in operating activities for the years ended December 31, 2025 and 2024 was $77.2 million and $158.3 million, respectively. Our future ability to generate cash from operations will depend on achieving regulatory approval and market acceptance of our product candidates, achieving benchmarks as defined in existing collaboration agreements, and our ability to enter into new collaborations.
From our inception through December 31, 2024, we have raised aggregate net proceeds of approximately $2.01 billion through the sale of common and preferred stock, the exercise of stock options and warrants, proceeds from our Employee Stock Purchase Plan, royalty monetization transactions, and the issuance of convertible and other notes.
From our inception through December 31, 2025, we have raised aggregate net proceeds of approximately $2.05 billion through the sale of common and preferred stock, the exercise of stock options and warrants, proceeds from our Employee Stock Purchase Plan, royalty monetization transactions, and the issuance of convertible and other notes.
See Note 16 of the notes to our consolidated financial statements contained elsewhere in this Annual Report on Form 10-K for further description of our debt. (2) The leases for our properties expire at various times between 2025 and 2036.
See Note 17 of the notes to our consolidated financial statements contained elsewhere in this Annual Report on Form 10-K for further description of our debt. (2) The leases for our properties expire at various times between 2026 and 2036.
Our common stock is currently listed on The Nasdaq Capital Market under the symbol “AGEN.” Our research and development expenses for the years ended December 31, 2024, 2023, and 2022, were $155.5 million, $234.6 million, and $186.7 million, respectively. We have incurred significant losses since our inception. As of December 31, 2024, we had an accumulated deficit of $2.18 billion.
Our common stock is currently listed on The Nasdaq Capital Market under the symbol “AGEN.” Our research and development expenses for the years ended December 31, 2025, 2024, and 2023, were $79.3 million, $155.5 million, and $234.6 million, respectively. We have incurred significant losses since our inception. As of December 31, 2025, we had an accumulated deficit of $2.18 billion.
In November 2019, we entered into a license agreement with UroGen, granting them an exclusive, worldwide license (not including Argentina, Brazil, Chile, Colombia, Peru, Venezuela and their respective territories and possessions) to develop, manufacture, and commercialize zalifrelimab for the treatment of cancers of the urinary tract via intravesical delivery.
In November 2019, we entered into a license agreement with UroGen, granting them an exclusive, worldwide license (not including Argentina, Brazil, Chile, Colombia, Peru, Venezuela and their respective territories and possessions) to develop, manufacture, and commercialize zalifrelimab for the treatment of cancers of the urinary tract via intravesical delivery. We received an upfront payment of $10.0 million.
We currently have multiple antibody programs in pre-clinical or clinical development, which include our next generation anti-CTLA-4 antibody, botensilimab, an IgG1 anti-CTLA-4 antagonist, our anti-PD-1, balstilimab, and anti-CTLA-4, zalifrelimab, programs (both partnered with Betta in Greater China), our anti-CD137, AGEN2373, an anti-TIGIT bispecific antibody, AGEN1777, an ILT2 monospecific antibody, AGEN1571, an anti-LAG3, INCAGN2385, and anti-TIM3, INCAGN2390.
We currently have multiple antibody programs in pre-clinical or clinical development, which include our next generation anti-CTLA-4 antibody, botensilimab, an IgG1 anti-CTLA-4 antagonist, our anti-PD-1, balstilimab, and anti-CTLA-4, zalifrelimab, programs, our anti-CD137, AGEN2373, an anti-TIGIT bispecific antibody, AGEN1777, an ILT2 monospecific antibody, AGEN1571, an anti-LAG3, INCAGN2385, and anti-TIM3, INCAGN2390.
In June 2020, we entered into a license and collaboration agreement (the “Betta License Agreement”) with Betta, pursuant to which we granted Betta an exclusive license to develop, manufacture and commercialize balstilimab and zalifrelimab in Republic of China, Hong Kong, Macau and Taiwan (“Greater China”).
In June 2020, we entered into a license and collaboration agreement (the “Betta License Agreement”) with Betta, pursuant to which we granted Betta an exclusive license to develop, manufacture and commercialize balstilimab and zalifrelimab in Republic of China, Hong Kong, Macau and Taiwan (“Greater China”). Under the terms of the Betta License Agreement, we received $15.0 million upfront.
Non-cash royalty revenue related to our agreement with GSK decreased $13.6 million, to approximately $101.0 million for the year ended December 72 31, 2024, from $114.6 million for the year ended December 31, 2023, due to decreased net sales of GSK’s vaccines containing our QS-21 STIMULON adjuvant.
Non-cash royalty revenue related to our agreement with GSK increased $7.6 million, to approximately $108.6 million for the year ended December 31, 2025, from $101.0 million for the year ended December 31, 2024, due to increased net sales of GSK’s vaccines containing our QS-21 STIMULON adjuvant.
Upon termination the rights to the remaining programs will revert back to us. Pursuant to our collaboration and license agreement with Merck, we exclusively licensed MK-4830 to Merck, which Merck advanced in a Phase 2 clinical trial.
Upon termination, the rights to the remaining programs reverted back to us. 68 Pursuant to our collaboration and license agreement with Merck, we exclusively licensed to Merck a monospecific antibody targeting ILT4 (MK-4830), which Merck advanced in a Phase 2 clinical trial.
These decreases were partially offset by a $3.2 million increase in other research and development expenses. General and administrative expense General and administrative (“G&A”) expense consists primarily of personnel costs, facility expenses, and professional fees. G&A expense decreased 9% to $71.9 million for the year ended December 31, 2024 from $78.7 million for the year ended December 31, 2023.
These decreases were partially offset by a $0.2 million increase in professional fees. General and administrative expense General and administrative (“G&A”) expense consists primarily of personnel costs, facility expenses, and professional fees. G&A expense decreased 24% to $54.4 million for the year ended December 31, 2025 from $71.9 million for the year ended December 31, 2024.
Under these agreements, subject to the enrollment of patients and performance by the applicable third-party provider, we have estimated our total payments to be $660.7 million over the term of the related activities. Through December 31, 2024, we have expensed $616.5 million as research and development expenses and $578.3 million has been paid under these agreements.
Under these agreements, subject to the enrollment of patients and performance by the applicable third-party provider, we have estimated our total payments to be $687.0 million over the term of the related activities. Through December 31, 2025, we have expensed $628.0 million as research and development expenses and $574.6 million has been paid under these agreements.
However, because the completion of cash funding transactions is not entirely within our control, and in accordance with accounting standards, substantial doubt continues to exist about our ability to continue as a going concern for a period of one year after the date of filing of this Annual Report on Form 10-K.
Because the completion and timing of potential financing and strategic transactions are not entirely within our control, and in accordance with accounting standards, substantial doubt exists about our ability to continue as a going concern for at least one year after the date of filing of this Annual Report on Form 10-K.
We have entered into collaborations with several companies, including Bristol-Myers Squibb Company (“BMS”), Betta Pharmaceuticals Co., Ltd. (“Betta”), UroGen Pharma Ltd. (“UroGen”), Gilead Sciences, Inc. (“Gilead”), Incyte Corporation (“Incyte”), and Merck Sharp & Dohme (“Merck”). These collaborations, along with our internal programs, have resulted in over a dozen antibody pre-clinical or clinical development programs.
(“Betta”), UroGen Pharma Ltd. (“UroGen”), Gilead Sciences, Inc. (“Gilead”), Incyte Corporation (“Incyte”), and Merck Sharp & Dohme (“Merck”). These collaborations, along with our internal programs, have resulted in over a dozen antibody pre-clinical or clinical development programs.
Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations Overview Agenus Inc. (including its subsidiaries, collectively referred to as “Agenus,” the “Company,” “we,” “us,” and “our”) is a clinical-stage biotechnology company specializing in discovering and developing therapies to activate the body's immune system against cancer and infections.
Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations Overview Agenus Inc. (including its subsidiaries, collectively referred to as “Agenus,” the “Company,” “we,” “us,” and “our”) is a clinical-stage biotechnology company focused on discovering and developing immunotherapies for cancer and infectious disease.
After taking into account our obligations under the Ligand Purchase Agreement, XOMA Royalty Purchase Agreement and the recent status of our collaboration agreements, we remain eligible to receive up to approximately $136.3 million and $49.4 million in potential development, regulatory, and commercial milestones from UroGen and Merck, respectively.
The synthetic royalty can increase by 1% based on the occurrence of certain future events. After taking into account our obligations under the Ligand Purchase Agreement, XOMA Royalty Purchase Agreement and the recent status of our collaboration agreements, we remain eligible to receive up to approximately $49.4 million in potential development, regulatory, and commercial milestones from Merck.
We sold approximately 3.6 million and 1.6 million shares of our common stock pursuant to the Sales Agreement during the year ended December 31, 2024 and the period of January 1, 2025 through March 13, 2025, respectively, and received aggregate net proceeds totaling $37.5 million.
We sold approximately 9.7 million and 0.2 million shares of our common stock pursuant to the Sales Agreement during the year ended December 31, 2025 and the period of January 1, 2026 through March 12, 2026, respectively, and received aggregate net proceeds totaling $36.9 million.
R&D expense decreased 34% to $155.5 million for the year ended December 31, 2024 from $234.6 million for the year ended December 31, 2023.
R&D expense decreased 49% to $79.3 million for the year ended December 31, 2025 from $155.5 million for the year ended December 31, 2024.
Since inception, we have entered into various cancelable agreements with contract manufacturers, institutions, and clinical research organizations (collectively "third party providers") to perform pre-clinical activities and to conduct and monitor our clinical studies.
Our future cash requirements include, but are not limited to, supporting clinical trial and regulatory efforts and continuing our other research and development programs. Since inception, we have entered into various cancelable agreements with contract manufacturers, institutions, and clinical research organizations (collectively "third party providers") to perform pre-clinical activities and to conduct and monitor our clinical studies.
Decreased R&D expenses in the year ended December 31, 2024 primarily relate to a $52.7 million decrease in third-party services and other expenses, largely due to the timing of expenses related to the advancement of our antibody programs, a $11.4 million decrease in personnel related expenses, mainly due to a decrease in headcount, and a $18.1 million decrease in expenses attributable to the activities of our subsidiaries.
Decreased R&D expenses in the year ended December 31, 2025 primarily relate to a $51.9 million decrease in third-party services and other expenses, largely due to the timing of expenses related to the advancement of our antibody programs, a $14.3 million decrease in personnel related expenses, mainly due to a decrease in headcount, a $2.0 million decrease in 70 other research and development expenses, and a $7.9 million decrease in expenses attributable to the activities of our subsidiaries, which decrease is partially attributable to the deconsolidation of MiNK.
As of March 13, 2025, approximately 16.5 million shares remained available for sale under the Sales Agreement. Our cash, cash equivalents and short-term investments at December 31, 2024 were $40.4 million, a decrease of $35.7 million from December 31, 2023. Since year end, we have raised $4.4 million through at-the-market sales.
As of March 12, 2026, approximately 8.2 million shares remained available for sale under the Sales Agreement. Our cash, cash equivalents and short-term investments at December 31, 2025 were $3.0 million, a decrease of $37.4 million from December 31, 2024.
The financial statements have been prepared on a basis that assumes Agenus will continue as a going concern and which contemplates the realization of assets and satisfaction of liabilities and commitments in the ordinary course of business. Management continues to diligently address the Company’s liquidity needs and has continued to adjust spending in order 75 to preserve liquidity.
The consolidated financial statements have been prepared assuming we will continue as a going concern and which contemplates the realization of assets and satisfaction of liabilities and commitments in the ordinary course of business. Management has also implemented cost management measures to preserve liquidity.
Decreased G&A expenses in the year ended December 31, 2024 primarily relate to a $4.6 million decrease in personnel related expenses, mainly due to decreased share based compensation expense and a decrease in headcount, a $0.3 million decrease in professional fees and a $3.3 million decrease in expenses attributable to the activities of our subsidiaries.
Decreased G&A expenses in the year ended December 31, 2025 primarily relate to a $9.1 million decrease in personnel related expenses, mainly due to a decrease in headcount, a $3.4 million decrease other general and administrative expenses and a $5.1 million decrease in expenses attributable to the activities of our subsidiaries, which decrease is partially attributable to the deconsolidation of MiNK.
For the Year Ended December 31, Research and Development Program Product 2024 2023 2022 Prior to 2022 Total Antibody programs Various $ 113,135 $ 178,445 $ 133,108 $ 739,165 $ 1,163,853 Vaccine adjuvant STIMULON cpcQS-21 1,844 10,296 10,789 21,397 44,326 Cell therapies Various 7,558 16,283 24,300 61,129 109,270 Other research and development programs Various 32,991 29,545 18,494 477,091 558,121 Total research and development expenses $ 155,528 $ 234,569 $ 186,691 $ 1,298,782 1,875,570 Research and development program costs include compensation and other direct costs plus an allocation of indirect costs, based on certain assumptions and our review of the status of each program.
For the Year Ended December 31, Research and Development Program Product 2025 2024 2023 Prior to 2023 Total Antibody programs Various $ 55,493 $ 113,135 $ 178,445 $ 872,273 $ 1,219,346 Vaccine adjuvant STIMULON cpcQS-21 1,638 1,844 10,296 32,186 45,964 Cell therapies Various 3,282 7,558 16,283 85,429 112,552 Other research and development programs Various 18,925 32,991 29,545 495,585 577,046 Total research and development expenses $ 79,338 $ 155,528 $ 234,569 $ 1,485,473 1,954,908 71 Research and development program costs include compensation and other direct costs plus an allocation of indirect costs, based on certain assumptions and our review of the status of each program.
We received an upfront payment of $10.0 million and are eligible to receive up to $200.0 million in milestone payments, as well as royalties on future sales.
Merck is responsible for all future development expenses, and we are eligible to receive up to an additional $85.0 million in potential milestone payments, as well as royalties on future sales.
Interest expense, net Interest expense, net increased to $117.6 million for the year ended December 31, 2024 from $97.9 million for the year ended December 31, 2023, mainly due to increased non-cash interest recorded in connection with our Royalty Purchase Agreement with HCR and the addition of non-cash interest expense recorded in connection with our Ligand Purchase Agreement.
Interest expense, net Interest expense, net decreased to $55.3 million for the year ended December 31, 2025 from $117.6 million for the year ended December 31, 2024, mainly due to decreased non-cash interest recorded in connection with our Royalty Purchase Agreement with HCR, primarily attributable to decreased sales forecasts of GSK’s vaccines containing our STIMULON QS-21 adjuvant, partially offset by an increase of the non-cash interest expense recorded in connection with our Ligand Purchase Agreement.
BMS received an exclusive worldwide license to develop, manufacture, and commercialize AGEN1777 and its derivatives. We received a non-refundable upfront cash payment of $200.0 million.
In 2025, we notified Betta of the termination of the Betta License Agreement. In May 2021, we entered into a License, Development, and Commercialization Agreement with BMS for our pre-clinical anti-TIGIT bispecific antibody program, AGEN1777. BMS received an exclusive worldwide license to develop, manufacture, and commercialize AGEN1777 and its derivatives. We received a non-refundable upfront cash payment of $200.0 million.
As of December 31, 2024, we had debt outstanding of $35.2 million in principal, $2.5 million of which was paid in February 2025, $10.5 million is due July 2026, and $22.0 million is due November 2026.
As of December 31, 2025, we had debt outstanding of $45.5 million in principal, $8.4 million of which was paid and $7.0 million of which was forgiven in connection with close of the Zydus transactions in January 2026, $5.1 million is due June 2026, and $24.75 million is due November 2026.
Based on the BOT/BAL clinical data generated to date, we have developed designs for registration-enabling trials in MSS CRC across neoadjuvant, first-line, and late-line mCRC. These trial(s) will launch upon completion of strategic transactions. The options being considered are partnerships, licensing, or joint ventures.
Based on the BOT/BAL clinical data generated to date, we have developed designs for registration-enabling trials in Microsatellite Stable colorectal cancer across neoadjuvant, first-line, and late-line metastatic colorectal cancer.
“Business” of this Annual Report on Form 10-K.
“Business” of this Annual Report on Form 10-K. Cell Therapies We have a significant equity investment in MiNK.
Payments by Period Total Less than 1 Year 1-3 Years 3-5 Years More than 5 Years Long-term debt (1) $ 37,459 $ 3,660 $ 33,799 $ — $ — Operating leases (2) 101,419 8,609 16,819 17,667 58,324 Finance leases 5,002 4,879 123 — — Total $ 143,880 $ 17,148 $ 50,741 $ 17,667 $ 58,324 (1) Includes fixed interest payments.
Payments by Period Total Less than 1 Year 1-3 Years 3-5 Years More than 5 Years Long-term debt (1) $ 36,764 $ 36,764 $ — $ — $ — Operating leases (2) $ 16,897 $ 2,396 $ 4,897 $ 4,505 $ 5,099 Finance leases $ 127 $ 110 $ 17 $ — $ — Total $ 53,788 $ 39,270 $ 4,914 $ 4,505 $ 5,099 (1) Includes fixed interest payments.
Removed
Our pipeline includes immune-modulatory antibodies, adoptive cell therapies (via MiNK Therapeutics, Inc. ("MiNK")), and vaccine adjuvants (via SaponiQx, Inc. ("SaponiQx")). Our primary focus is immuno-oncology (“I-O”), and our diverse pipeline is supported by our in-house capabilities, including current good manufacturing practice (“cGMP”) manufacturing and a clinical operations platform. To succeed in I-O, innovation and speed are paramount.
Added
Our primary business is immuno-oncology ("I-O"), where we are advancing antibody-based programs to activate innate and adaptive immunity, overcome tumor immune evasion and expand the population of patients who may benefit from immunotherapy. Our lead clinical program is botensilimab (“BOT” or “AGEN1181”), alone and in combination with balstilimab (“BAL”).
Removed
We are a vertically integrated biotechnology company equipped with a suite of technology platforms to advance from novel target identification through manufacturing for clinical trials of antibodies and cell therapies. By understanding each patient's cancer, we aim to substantially expand the population benefiting from current I-O therapies.
Added
We also maintain select clinical-stage immuno-oncology assets, which may be used as standalone agents or be complimentary to botensilimab plus balstilimab (“BOT/BAL”). Agenus also maintains an equity investment in MiNK Therapeutics, Inc. ("MiNK"), with an approximate fair value of $24.3 million as of December 31, 2025, and a majority ownership of a vaccine adjuvant business through our subsidiary SaponiQx, Inc.
Removed
In addition to a diverse pipeline, we have assembled fully integrated end-to-end capabilities including novel target discovery, antibody generation, cell line development and cGMP manufacturing. Leveraging our science and capabilities, we have established strategic partnerships to advance innovation.
Added
("SaponiQx"). We use internal discovery, translational, clinical and regulatory capabilities together with selected collaborations to advance product candidates. Following our strategic realignment announced in December 2024, we prioritized the botensilimab/balstilimab program and temporarily paused certain non-core preclinical and clinical activities while we evaluate partnering, as well as targeted funding opportunities.
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We believe the next generation of cancer treatment will build on clinically validated antibodies targeting CTLA-4 and PD-1 combined with novel immunomodulatory agents designed to address underlying tumor escape mechanisms.
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We, together with the Canadian Cancer Trials Group (“CCTG”), are conducting BATTMAN/CO.33, a global Phase 3 trial of botensilimab plus balstilimab versus best supportive care in refractory MSS/mismatch repair proficient ("pMMR") colorectal cancer, with sites activated and prepared to enroll patients. We have entered into collaborations with several companies, including Bristol-Myers Squibb Company (“BMS”), Betta Pharmaceuticals Co., Ltd.
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Under the terms of the Betta License Agreement, we received $15.0 million upfront and are eligible to receive up to $100.0 million in milestone payments plus royalties on any future sales in Greater China. In May 2021, we entered into a License, Development, and Commercialization Agreement with BMS for our pre-clinical anti-TIGIT bispecific antibody program, AGEN1777.
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In November 2025 Urogen notified us they were terminating the license agreement in accordance with the terms of the agreement.
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The synthetic royalty can increase by 1% based on the occurrence of certain future events.
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Management’s Discussion and Analysis of Financial Condition and Results of Operations” filed on March 17, 2025.
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MiNK’s most advanced product candidate, agenT-797, is an off-the-shelf, allogeneic, native iNKT cell therapy. MiNK is currently expanding its clinical programs, with an externally funded Phase 2 trial in second-line gastric cancer actively enrolling at Memorial Sloan Kettering Cancer Center.
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Year Ended December 31, 2025 Compared to the Year Ended December 31, 2024 Pre-commercial product revenue We recognized pre-commercial product revenue of approximately $4.2 million during the year ended December 31, 2025, representing sales of BOT+BAL provided to patients through regulatory-authorized early access pathways under both France’s Authorisation d’Accès Compassionnel ("AAC") framework and paid named patient programs ("NPPs"), where permitted.
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Additionally, MiNK is evaluating agenT-797 as a variant-agnostic therapy for patients with viral acute respiratory distress syndrome (“ARDS”) in planning for a randomized Phase 2 study through a predominantly externally financed program. In May 2024, MiNK secured a $5.8 million private placement financing at a 25% premium, led by GKCC, LLC.
Added
Gain from deconsolidation of MiNK Therapeutics, Inc. The gain from deconsolidation of MiNK Therapeutics, Inc. of $100.9 million for the year ended December 31, 2025, represents the gain recognized on the deconsolidation of MiNK due to a loss of control in the third quarter of 2025.
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This funding will be used for the clinical development of MiNK-215, its leading allogeneic CAR-iNKT cell therapy targeting fibroblast activation protein (“FAP”) in solid tumors, which is scheduled to enter clinical trials in early 2025. In addition to its lead clinical program, MiNK has announced a collaboration with ImmunoScape, Inc.
Added
MiNK Therapeutics, Inc. equity method investment fair value adjustment The MiNK Therapeutics, Inc. equity method investment fair value adjustment of $26.3 million for the year ended December 31, 2025, represents the fair value adjustment for our remaining investment in MiNK, for which we have elected the fair value option.
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(“ImmunoScape”) to discover and develop next-generation T-cell receptor therapies targeting novel solid tumor antigens. This partnership leverages MiNK’s proprietary library of T-cell antigens and ImmunoScape’s platform for rapid discovery of novel T-cell receptors.
Added
The fair value of our equity investment is based on readily determinable pricing available on a securities exchange.
Removed
Management’s Discussion and Analysis of Financial Condition and Results of Operations” filed on March 14, 2024. Year Ended December 31, 2024 Compared to the Year Ended December 31, 2023 Research and development revenue We recognized research and development (“R&D”) revenue of approximately $0.5 million and $38.8 million during the years ended December 31, 2024 and 2023, respectively.
Added
Subsequent to December 31, 2025, including cash received in January 2026, we materially strengthened our liquidity position. MiNK Therapeutics repaid a $5.2 million related-party note receivable, and we closed agreements with Zydus Lifesciences Ltd. and its affiliates, pursuant to which we received $91.0 million of consideration, subject to certain adjustments.
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R&D revenues for the year ended December 31, 2023, primarily consisted of a $25.0 million milestone earned under our BMS License Agreement and $12.2 million related to the recognition of deferred revenue earned under our Gilead Collaboration Agreements.
Added
These adjustments include reimbursable expenses, other required closing payments, including approximately $5.8 million of transaction expenses, and $7.5 million placed into a twelve-month escrow. See Note 23 for further discussion of the proceeds received and liabilities settled in connection with the Zydus closing.
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These decreases were partially offset by a $1.3 million increase in other general and administrative expenses. Fair value adjustments For the year ended December 31, 2024, the fair value adjustment represents the change in fair value of the Purchaser Upsize Option issued under the Ligand Purchase Agreement.
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As of December 31, 2025, before giving effect to these post-year-end proceeds, we had cash and cash equivalents of $3.0 million, compared with $40.4 million as of December 31, 2024. Since our inception in 1994, we have incurred significant operating losses, and as of December 31, 2025, we had an accumulated deficit of $2.18 billion.
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The fair value of the Purchaser Upsize Option is based on a scenario analysis and uses assumptions we believe would be made by a market participant. For the year ended December 31, 2023, the fair value adjustment represents the change in the fair value of our contingent purchase price consideration.
Added
Based on our current operating plan and projections, including payment of debt due in the look-forward period, the majority of which is secured by certain real estate properties, and assuming completion of additional capital transactions of which we are in current discussions, we believe that our existing cash resources, together with the post-year-end proceeds described above and anticipated revenues from our reimbursed compassionate access program in France, would be sufficient to support our critical liquidity requirements into 2027.
Removed
The fair value of our contingent purchase price considerations is mainly based on estimates from a Monte Carlo simulation of our share price.
Added
To advance our planned registration and commercialization strategy for botensilimab/balstilimab, and fund the Company through achievement of profitability, we will require additional capital infusions. We have historically financed our operations through corporate partnerships, advance royalty transactions, and debt and equity financings.
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Cash and cash equivalents of our subsidiary, MiNK, at September 30, 2024, were $6.3 million. MiNK cash can only be accessed by Agenus through a declaration of a dividend by the MiNK Board of Directors or through settlement of intercompany balances.
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We are actively evaluating and pursuing additional financing and strategic alternatives, including corporate transactions, out-licensing arrangements, asset sales, project financing, additional debt or equity financings, and other strategic transactions, and we are in discussions with potential strategic and financial partners regarding several of these alternatives.
Removed
Based on our current plans and projections, we believe our cash resources of $40.4 million as of December 31, 2024, along with additional cash inflows we may receive in 2025, will be sufficient to satisfy our critical liquidity requirements through the second quarter of 2025. To support operations on an ongoing basis we require additional funding.
Removed
Since our founding we have financed our operations principally through income and revenues generated from corporate partnerships, advance royalty sales, and proceeds from debt and equity issuances. We transact at-the-market sales from time to time in order to manage our cash balances. We execute at-the-market offerings based on market conditions and our stock price.
Removed
We do not have in place a program whereby at-the-market offerings are executed automatically based on our trading volume. Currently we are in discussions with entities including operating companies and financial entities to provide the funding necessary to support our operations through our planned registration and launch strategy for botensilimab/balstilimab.

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Item 7A. Quantitative and Qualitative Disclosures About Market Risk

Market Risk — interest-rate, FX, commodity exposure

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Biggest changeWe do not currently employ specific strategies, such as the use of derivative instruments or hedging, to manage these exposures.
Biggest changeWe do not currently employ specific strategies, such as the use of derivative instruments or hedging, to manage these exposures. Our currency exposures vary but are primarily concentrated in the British Pound, in large part due to our subsidiary, Agenus UK Limited, a company with operations in England.
Due to the short-term nature of our investments in money market funds, our carrying value approximates the fair value of these investments at December 31, 2024, however, we are subject to investment risk. We invest our cash and cash equivalents in accordance with our investment policy.
Due to the short-term nature of our investments in money market funds, our carrying value approximates the fair value of these investments at December 31, 2025, however, we are subject to investment risk. We invest our cash and cash equivalents in accordance with our investment policy.
Accordingly, we do not believe that there is currently any material market risk exposure with respect to derivatives or other financial instruments that would require disclosure under this item. 78
Accordingly, we do not believe that there is currently any material market risk exposure with respect to derivatives or other financial instruments that would require disclosure under this item. 76
Approximately 2.1% and 1.0% of our cash used in operations for the years ended December 31, 2024 and 2023, respectively, was from our foreign subsidiaries. We are exposed to foreign currency exchange rate fluctuation risk related to our transactions denominated in foreign currencies.
Approximately 4.7% and 2.1% of our cash used in operations for the years ended December 31, 2025 and 2024, respectively, was from our foreign subsidiaries. We are exposed to foreign currency exchange rate fluctuation risk related to our transactions denominated in foreign currencies.
We had cash and cash equivalents at December 31, 2024 of $40.4 million, which are exposed to the impact of interest and foreign currency exchange rate changes, and our interest income fluctuates as interest rates change. Additionally, in the normal course of business, we are exposed to fluctuations in interest rates as we seek debt financing and invest excess cash.
We had cash and cash equivalents at December 31, 2025 of $3.0 million, which are exposed to the impact of interest and foreign currency exchange rate changes, and our interest income fluctuates as interest rates change. Additionally, in the normal course of business, we are exposed to fluctuations in interest rates as we seek debt financing and invest excess cash.
Removed
Our currency exposures vary but are primarily concentrated in the British Pound and Swiss Franc, in large part due to our subsidiaries, Agenus UK Limited and AgenTus Therapeutics Limited, both with operations in England, and Antigenics SA, a company with operations in Switzerland.

Other AGEN 10-K year-over-year comparisons