About Agenus

Agenus Inc. (Agenus) operates as a clinical-stage company. The company has a pipeline of therapies designed to activate the body’s immune system to fight cancer and infections, including immune-modulatory antibodies, adoptive cell therapies (through its subsidiary MiNK Therapeutics, Inc. (MiNK)) and vaccine adjuvants (through its subsidiary SaponiQx, Inc. (SaponiQx)). This robust product pipeline is supported by the company’s in-house capabilities, including current good manufacturing practice (cGMP) manufacturing and a clinical operations platform. The company’s primary focus is immuno-oncology (I-O), and its business is designed to drive success through speed, innovation and effective combination therapies. The company’s most advanced antibody candidates are botensilimab (a proprietary next-generation Fc-engineered CTLA-4 antibody, also known as AGEN1811) and balstilimab (a PD-1 antibody). Botensilimab is designed to improve the magnitude of responses to first-generation CTLA-4 antibodies, to expand the population of patients benefiting from CTLA-4 therapy, and to reduce or eliminate side effects that lead to treatment discontinuation. Botensilimab is in three Phase 2 studies as a monotherapy (melanoma), in combination with chemotherapy (pancreatic cancer), and in combination with balstilimab (microsatellite stable colorectal cancer (MSS CRC)). The company reported updated data from the Phase 1b study at the American Society of Clinical Oncology – Gastrointestinal Cancers Symposium (ASCO GI) in January 2023, which demonstrated an overall response rate (ORR) of 23% and disease control rate (DCR) of 76% for the botensilimab/balstilimab combination in an expanded cohort of 70 heavily pre-treated patients with MSS CRC, which suggests a superior benefit compared to what has been reported for standard of care (SOC) and other investigational therapies. At the Society for Immunotherapy Cancer (SITC) meeting in November 2022, the company reported response rates of 26% for platinum-refractory ovarian cancer, 42% for advanced sarcoma, and 60% for anti-PD(L)-1 relapsed/refractory non-small cell lung cancer (“NSCLC”), all exceeding the response rates that have been reported for other PD-(L)1 + CTLA-4 combination regimens in comparable patient populations. In total, botensilimab alone and in combination with balstilimab have demonstrated durable clinical responses across nine cold and treatment-resistant cancers. Balstilimab and zalifrelimab, the company’s first generation CTLA-4 antibody, have been evaluated in Phase 2 trials as both a monotherapy (balstilimab) and combination therapy (balstilimab/zalifrelimab) for the treatment of patients with second-line cervical cancer. Both trials met their clinical endpoints. In addition to its lead programs, Agenus scientists have leveraged the company’s internal discovery and translational platforms and powerful algorithms to develop a pipeline of molecules that are intended to address key aspects of antitumor immunity and tumor resistance mechanisms, by modulating myeloid cell biology, conditioning the tumor microenvironment, and augmenting the activity of immune cells. Additionally, in October 2021, the comopany completed the initial public offering (IPO) of MiNK, trading on the Nasdaq Global Market under the ticker 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. MiNK’s most advanced product candidate, agenT-797, is an off-the-shelf, allogeneic, native iNKT cell therapy. MiNK has commenced and enrolled a Phase 1 clinical trial for the treatment of solid tumors as a monotherapy and in combination with commercially approved checkpoint inhibitors (KEYTRUDA and OPDIVO). MiNK is also evaluating agenT-797 as a variant-agnostic therapy for patients with viral acute respiratory distress syndrome (ARDS) and published top-line data from this Phase 1 clinical trial in the fourth quarter of 2021, reporting a 77% survival rate in older, mechanically ventilated patients with COVID-19 respiratory failure. The company is 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. Strategy The company’s strategy is to bring innovative combination therapies for cancer patients to substantially expand the patient population benefiting from current I-O therapies. The company’s diverse pipeline of antibody-based therapeutics, cell therapies, and vaccine adjuvants enable it to pursue therapeutically relevant approaches focused on safe and effective therapeutic agent combinations. In line with this approach, the company is pursuing clinical trials designed to strengthen the efficacy and safety signals demonstrated to date and that may support a potential filing for full approval and/or accelerated approval based on the magnitude of benefit demonstrated. The company’s strategies for its more novel, earlier stage development programs are to leverage learnings from prior programs to address limitations of first-generation molecules and build a portfolio that addresses resistance mechanisms. The company’s clinical portfolio also includes a number of differentiated approaches to novel I-O targets, including TIGIT, LAG-3, ILT4, ILT2, and CD137. For example, its CD137 agonist, AGEN2373, was designed to be conditionally active in the tumor microenvironment and has demonstrated clinical activity without evidence of liver toxicity that have stalled other clinical-stage CD137 therapies. These agents are being pursued in PD-1 combinations, as well as unique combinations driven by biology and clinical experience, such as its combination study evaluating botensilimab with CD137 (AGEN2373) antibodies in PD-1 relapsed or refractory melanoma. The company is advancing its portfolio through a combination of independent development and strategic partnerships with industry leaders. Assets The company’s I-O assets include antibody-based therapeutics, monospecific and bispecific antibodies, cell therapy (through MiNK), vaccine adjuvants (through SaponiQx). The company’s clinical-stage portfolio includes the following assets: Botensilimab (AGEN1181) – a next-generation CTLA-4 monospecific antibody currently three Phase 2 studies in MSS CRC, pancreatic cancer and melanoma as a monotherapy and in combination with balstilimab or chemotherapy; Balstilimab (AGEN2034) – a PD-1 monospecific antibody being evaluated in combinations with botensilimab and zalifrelimab, as well as in a clinical collaboration with Rottapharm S.p.A. in combination with CR6086; Zalifrelimab (AGEN1884) – a first-generation CTLA-4 monospecific antibody being evaluated in combination with balstilimab, as well as in a clinical collaboration with Nelum in combination with NLM-001; AGEN2373 – a CD137 monospecific antibody in a Phase 1b clinical trial being advanced by Agenus as monotherapy and in combination with botensilimab, and which Gilead Sciences, Inc. (Gilead) has an option to license exclusively; AGEN1423 – a tumor microenvironment conditioning CD73/TGFß TRAP bifunctional antibody that completed a Phase 1 clinical trial sponsored by Gilead; AGEN1571 – an ILT2 monospecific antibody in a Phase 1 clinical trial that the company is advancing as monotherapy and in combination with botensilimab and balstilimab in solid tumors; MK-4830 – a monospecific antibody targeting ILT4 exclusively licensed to Merck Sharpe & Dohme (Merck) and being evaluated by Merck in Phase 2 clinical trials in late stage cancers, including esophageal cancer, melanoma, MSI-H colorectal cancer, NSCLC, small cell lung cancer, ovarian cancer, and renal cell carcinoma; INCAGN1876 – a GITR monospecific antibody exclusively licensed to Incyte Corporation (Incyte) and being advanced by Incyte in a Phase 2 clinical trial evaluating INCAGN1876 in combination with retifanlimab in squamous cell carcinoma of the head and neck; INCAGN2390 – a TIM-3 monospecific antibody exclusively licensed to Incyte and being advanced by Incyte in Phase 2 clinical trials evaluating INCAGN2385 and INCAGN2390 in combination with retifanlimab in melanoma, squamous cell carcinoma of the head and neck, and endometrial cancer; INCAGN2385 – a LAG-3 monospecific antibody exclusively licensed to Incyte and being advanced by Incyte in Phase 2 clinical trials evaluating INCAGN2385 and INCAGN2390 in combination with retifanlimab in melanoma, squamous cell carcinoma of the head and neck, and endometrial cancer; BMS-986442 (also known as AGEN1777) – a TIGIT bispecific discovered by Agenus and exclusively licensed to Bristol Myers Squibb Company (“BMS”) and being advanced by BMS in a Phase 1/2 clinical trial evaluating BMS-986442 in combination with nivolumab +/- chemotherapy in patients with advanced solid tumors and non-small cell lung cancer; UGN-301 – zalifrelimab intravesical solution, prepared as a reverse thermal hydrogel, exclusively licensed to UroGen Pharma (UroGen) for the treatment of cancers of the urinary tract via intravesical delivery and being advanced by UroGen in a Phase 1 clinical trial as a monotherapy and in combination with other agents, including UGN-201; agenT-797 – allogeneic iNKT cells exclusively licensed to MiNK and being advanced by MiNK in Phase 1 studies in solid tumors, multiple myeloma, and viral ARDS; and QS-21 STIMULON – adjuvant extracted from the bark of the Quillaja saponaria (soap bark) evergreen tree native and purified using the company’s proprietary process; key component in the adjuvant in several GlaxoSmithKline plc (GSK) vaccines, including the most efficacious shingles vaccine, Shingrix, which has demonstrated >90% efficacy, as well as the first ever malaria vaccine, Mosquirix, and recent RSV vaccine. The company’s proprietary QS-21 STIMULON is considered to be one of the most potent adjuvants known. By way of example, QS-21 STIMULON is a key component in the adjuvant in several GSK vaccines, including GSK’s Shingrix. Antibody Discovery Platforms and Immunotherapy Programs The company’s pipeline includes several classes of immunotherapies: checkpoint inhibitors, which remove the tumor’s defenses that evade and suppress the immune system; immune activators, which train and activate a patient’s own immune cells for a potent and durable anti-cancer response; and tumor microenvironment (TME) conditioning agents, which reduce local immune-suppression and attract immune cells to the cancer site. The company possesses end-to-end capabilities in-house – from discovery through to manufacturing – that have enabled it to advance its discoveries at lower costs with efficiency and speed. These product development advantages allow the company to manage a large portfolio of discoveries; and have given rise to clinical stage antibody candidates, pre-clinical programs, and partnerships (i.e., with BMS, Gilead, Incyte, Merck, GSK and Betta Pharmaceuticals Co., Ltd. (Betta)). Partnered Programs In May 2021, the company entered into a License, Development and Commercialization Agreement with BMS (the BMS License Agreement) pursuant to which it granted BMS an exclusive license to develop, manufacture and commercialize its proprietary TIGIT bispecific antibody program AGEN1777. In June 2020, the company entered into a license and collaboration agreement (the Betta License Agreement) with Betta, pursuant to which it granted Betta an exclusive license to develop, manufacture and commercialize balstilimab and zalifrelimab in the People’s Republic of China, Hong Kong, Macau and Taiwan (collectively, Greater China). In December 2018, the company entered into a series of agreements with Gilead to collaborate on the development and commercialization of up to five novel I-O therapies. In the third quarter of 2021, the company ceased development of AGEN1223 and in October 2021, the AGEN1223 option and license agreement was formally terminated. The AGEN2373 option and license agreement and the stock purchase agreement remain in full force and effect, and it is responsible for developing AGEN2373 up to the option decision point, at which time Gilead may acquire exclusive rights to the program on option exercise. In January 2015, the company entered into a collaboration with Incyte to discover, develop and commercialize novel immuno-therapeutics using its antibody platforms. In April 2014, the company entered into a collaboration and license agreement with Merck to discover and optimize fully-human antibodies against two undisclosed immunotherapy targets. In 2016, Merck selected a lead product candidate against ILT4, MK-4830, to advance into preclinical studies, and subsequently initiated a Phase 1 clinical trial in August 2018. In November 2020, Merck initiated a Phase 2 clinical trial with MK-4830. Under the terms of the agreement, Merck is responsible for all future product development expenses for MK-4830, and Agenus is eligible to receive potential milestone payments plus royalties on any future sales. On September 20, 2018, the company, through its wholly-owned subsidiary, Agenus Royalty Fund, LLC, entered into a Royalty Purchase Agreement (the XOMA Royalty Purchase Agreement) with XOMA (US) LLC (XOMA US). VISION VISION is an active learning platform that is intended to use a patient’s tumor, immune system, and health data to predict their best treatment options. Predictions are strengthened by laboratory experiments that interrogate how the company’s drugs perform under conditions that mimic a patient’s tumor and immune system. SaponiQx & QS-21 STIMULON Adjuvant QS-21 STIMULON is an adjuvant, which is a substance added to a vaccine or other immunotherapy that is intended to enhance an immune response to the target antigens. QS-21 STIMULON is a natural product, a triterpene glycoside, or saponin, purified from the bark of the Chilean soapbark tree, Quillaja saponaria. QS-21 STIMULON has the ability to stimulate an antibody-mediated immune response and has also been shown to activate cellular immunity. It has become a key component in the development of investigational preventive vaccine adjuvants across a wide variety of diseases. 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 STIMULON 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. In September 2021, the company launched SaponiQx, its subsidiary building an integrated vaccine platform based on scalable and secure manufacturing of QS-21 STIMULON and other saponin-based adjuvants. The need for vaccines offering long-lasting efficacy and efficient production was amplified in the COVID-19 pandemic. The durability offered by QS-21 STIMULON has been validated by Shingrix, with protection exceeding nine years, but the supply is limited due to reliance on a complicated and expensive extraction process from a Chilean soap bark tree. To this end, SaponiQx is working with Phyton Biotech and Ginkgo Bioworks to optimize the plant cell culture process, which it has developed for the purposes of scalable manufacturing QS-21 and next-generation saponin based adjuvants. In January 2019, the company announced that the Bill & Melinda Gates Foundation awarded it a grant to develop the plant cell culture process for QS-21 STIMULON. Partnered QS-21 STIMULON Programs In 2006, the company 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). In 2009, the company 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. GSK is obligated to supply it, or its affiliates, licensees, or customers, certain quantities of commercial grade QS-21 STIMULON for a stated period of time. In March 2012, the company entered into a First Right to Negotiate and Amendment Agreement amending the GSK License Agreement and the Amended GSK Supply Agreement to clarify and include additional rights for the use of QS-21 STIMULON (the GSK First Right to Negotiate Agreement). Manufacturing Antibody Manufacturing In December 2015, the company acquired an antibody manufacturing pilot plant in Berkeley, CA from XOMA Corporation (XOMA), which it refers to as Agenus West. QS-21 STIMULON Except in the case of GSK, the company has retained worldwide manufacturing rights for QS-21 STIMULON, and it has the right to subcontract manufacturing for QS-21 STIMULON. In addition, under the terms of its agreement with GSK, upon request by the company, GSK is committed to supply certain quantities of commercial grade QS-21 STIMULON to it and its licensees for a fixed period. Intellectual Property Portfolio The company seeks to protect its technologies through a combination of patents, trade secrets and know-how, and it owns, co-owns or has exclusive rights to approximately 37 issued United States patents and approximately 124 issued foreign patents. The company also owns, co-owns or has exclusive rights to approximately 38 pending United States patent applications and approximately 317 pending foreign patent applications. Through various acquisitions, the company owns, co-owns, or has 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. In particular, the company owns patents and patent applications relating to its Retrocyte Display technology platform, a high throughput antibody expression platform for the identification of fully-human and humanized monoclonal antibodies. This patent family is projected to expire between 2029 and 2031. The company owns, co-owns, or has exclusive rights to patents and patent applications directed to various methods and compositions, including a patent directed to methods for identifying phosphorylated proteins using mass spectrometry. This patent is projected to expire in 2023. In addition, as the company advances its research and development efforts with its institutional and corporate collaborators, it is seeking patent protection for certain newly identified therapeutic antibodies and product candidates. Various patents and patent applications have been exclusively licensed to the company by the following entities: Ludwig Institute for Cancer Research On December 5, 2014, the company’s wholly-owned subsidiary, Agenus Switzerland Inc. (4-AB), entered into a license agreement with the Ludwig Institute for Cancer Research Ltd. (Ludwig), which replaced and superseded a prior agreement entered into between the parties in May 2011. Pursuant to the terms of the license agreement, Ludwig granted 4-AB 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. On January 25, 2016, the company and 4-AB entered into a second license agreement with Ludwig, on substantially similar terms, to develop CTLA-4 and PD-1 antibodies. Research and Development The company’s research and development expense included $186.7 million for the year ended December 31, 2022. Competition The company is aware of competitors with approved PD-1 and PD-L1 agents in ex-U.S. geographies, such as China. These include Innovent Biologics, Shanghai Junshi Biosciences (Coherus BioSciences has rights to co-develop in U.S. and Canada), Shanghai HengRui Pharmaceuticals, Beigene (Novartis has ex-China rights), CStone Pharmaceuticals (EQRx has ex-China rights), Gloria Biosciences (Arcus Bioscience has rights in North America, Europe, Japan and certain other territories), Alphamab Oncology/3D Medicines and Akeso Bio. The company is also aware of other competitors with clinical-stage PD-1/PD-L1 agents including but not limited to AbbVie, Amgen, Arcus Biosciences, Biocad Ltd., Boehringer Ingelheim, Checkpoint Therapeutics, CSPC ZhongQi Pharmaceutical Technology, Genor Biopharma/ Apollomics, Incyte, ImmuneOncia Therapeutics Inc., Janssen Pharmaceuticals, Lee’s Pharmaceuticals, Transcenta Holdings, Maxinovel Pharmaceuticals, Novartis, 3D Medicines, Qilu Pharmaceutical Co Ltd, Shanghai Henlius Biotech Co Ltd, Sinocelltech, Shandong New Time Pharmaceutical Co Ltd, and Lepu Biopharma. In addition, the company is also aware of anti-PD-(L)1 monospecific agents that are preclinical in stage. The company is also aware of competitors developing bispecifics targeting PD-1 or PD-L1. The company is aware of companies developing next-generation anti-CTLA-4 approaches. For example, BMS has a next-generation CTLA-4 program in the clinic, a peptide masked version of the non-fucosylated anti CTLA-4 antibody; the peptide masked version is designed to localize activity to the tumor and minimize systemic toxicity associated with parent drug. The company is also aware of other next-generation monospecifics targeting CTLA-4 in the clinic, including those from Harbour BioMed, OncoC4, Adagene, and Xilio Therapeutics. The company is also aware of companies advancing clinical stage, CTLA-4 targeting multispecifics as a next-generation approach, including, but not limited to, Macrogenics, Xencor, AstraZeneca, Akeso Biopharma and Alphamab. The company is also aware of competitors with clinical stage drug candidates against CTLA-4, GITR, LAG-3, TIM-3, CD73, TGFb, and CD137, in addition to those named earlier in this section. 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 the company’s investigational product candidates. In the United States, the FDA under the Federal Food, Drug, and Cosmetic Act, the Public Health Service Act and other federal statutes and regulations, subject pharmaceutical products to rigorous review. The company is subject to cGMP, GCP, and GLP compliance obligations and are subject to inspection by international regulatory authorities. The company is subject to regulation under the Occupational Safety and Health Act, the Toxic Substances Control Act, the Resource Conservation and Recovery Act, and other current and potential future federal, state, or local regulations. The company conducts its activities in compliance with the National Institutes of Health Guidelines for Recombinant DNA Research. History Agenus Inc. was founded in 1994. The company was incorporated in 1999. It was formerly known as Antigenics Inc. and changed its name to Agenus Inc. in 2011.