AGENUS INC

We are a clinical-stage biotechnology company specializing in discovering and developing therapies to activate the body's immune system against cancer and infections. 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. 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. 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. 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.

Our common stock is currently listed on The Nasdaq Capital Market under the symbol “AGEN.”

Our Vision

We envision a future where I-O combinations will unlock the full potential of cancer treatment and provide patients with significantly extended and improved lives. We believe our fully integrated, end-to-end capabilities for novel target discovery, antibody generation, and cell line development to our cGMP manufacturing and clinical development and operations capabilities, together with a comprehensive and complementary portfolio will uniquely position us to produce potential novel therapies on accelerated timelines.

Our Assets

Our assets encompass a comprehensive array of I-O therapeutics, including antibody-based treatments, monospecific and bispecific antibodies, cell therapy, and vaccine adjuvants. Notable components of our clinical-stage portfolio include botensilimab (“AGEN1181”), a human Fc-enhanced cytotoxic T-lymphocyte antigen 4 (“CTLA-4”) blocking antibody, currently in Phase 2 trials in metastatic colorectal cancer (“mCRC”), pancreatic cancer, and melanoma, both as a monotherapy and in combination with balstilimab or chemotherapy; balstilimab (“AGEN2034”), a programmed death receptor-1 (“PD-1”) blocking antibody being evaluated in various combinations; AGEN2373, a CD137 antibody in Phase 1b trials; AGEN1423, a CD73/TGFβ TRAP antibody; AGEN1571, an ILT2 antibody. We have also leveraged partnerships to advance our portfolio at speed and finance the business. These include INCAGN1876, INCAGN2390, and INCAGN2385, each targeting different receptors and formerly licensed to Incyte Corporation (“Incyte”); BMS-986442 (“AGEN1777”), a TIGIT bispecific antibody formerly licensed to Bristol Myers Squibb Company (“BMS”); and UGN-301, a zalifrelimab intravesical solution licensed to UroGen Pharma (“UroGen”). Finally, our subsidiary companies are advancing assets through exclusive licenses, including agenT-797, allogeneic invariant natural killer T (“iNKT”) cells licensed to MiNK; and QS-21 STIMULON, a cultured plant cell adjuvant used in various vaccines, including those by GlaxoSmithKline Biologicals, S.A. (“GSK”).

Our Clinical Pipeline Progress

Immunotherapies regulate the body’s immune response to cancer and have achieved positive outcomes in a number of cancers that were considered untreatable only a few years ago. Our clinical pipeline consists of various immunotherapy assets targeting complementary mechanisms to fight cancer including:

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.

Our most advanced antibody candidates are botensilimab (“BOT”) and balstilimab (“BAL”). BOT is a multifunctional immune cell activator and human CTLA-4 blocking antibody that engages with activating receptors on immune cells. BOT is designed to direct a more effective immune response to cancer through multiple mechanisms by enhancing T cell priming, activation and memory, upregulating antigen presenting cells and myeloid cells and reducing regulatory T cells. BOT also mitigates toxicities associated with first generation anti-CTLA-4 therapy, thus potentially expanding the patient population benefiting from treatment. Balstilimab (BAL)

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. When combined with BOT, BAL amplifies and sustains BOT-initiated responses and drives durability of tumor responses. We are investigating BOT as monotherapy and in combination with BAL, along with other mechanisms of action either within our own pipeline or those externally.

To date, BOT and BAL either as monotherapy treatment or as combination treatment have been evaluated in approximately 1,100 patients from more than 60 centers worldwide. The combination has demonstrated clinical responses across nine tumors including those historically considered I-O “cold” tumors resistant to earlier I-O treatments. 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. This designation specifically targets patients who are heavily pretreated and have shown resistance or intolerance to standard chemotherapies, including fluoropyrimidine, oxaliplatin, and irinotecan, as well as those who have received a VEGF inhibitor, an EGFR inhibitor, and/or a BRAF inhibitor, if indicated. We completed enrollment of the Phase 1 study which included patients with refractory MSS mCRC non-active liver metastases (“NLM”) in October 2023. Results from the Phase 1 study provided insights to the CRC patient population that may respond better to combination treatment of BOT/BAL, which provided foundation for the Phase 2 study population. 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. 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.

In January 2025, we presented results from the randomized, global Phase 2 trial in refractory MSS mCRC NLM versus standard treatments (regorafenib or trifluridine/tipiracil) at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium (“ASCO GI”) Annual Meeting in San Francisco demonstrating primary endpoints were met. The BOT75mg + BAL regimen demonstrated a 19% ORR and a 55% disease control rate (“DCR”) in this heavily pretreated population, while standard treatments showed no objective responses. Notably, 70% of responses were ongoing at data cut-off, indicating durable efficacy of the combination. BOT75mg + BAL exhibited a favorable benefit-risk profile and selected to advance in development. 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.

In addition to the Phase 2 company sponsored study in later line mCRC, data from multiple investigator sponsored trials (“ISTs”) were presented, investigating BOT/BAL in combination with FOLFOX and bevacizumab in metastatic CRC, and BOT/BAL in the neoadjuvant setting.

The neoadjuvant data presented at ASCO GI were from two independent studies - UNICORN and NEST. 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. 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. Pathological complete responses (“pCR”) and major responses (“pMR”) were observed in both pMMR/MSS and dMMR/MSI-H tumors, with dMMR/MSI-H patients achieving a 93% pCR and 100% pMR, while patients with pMMR/MSS CRC 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 delayed due to an adverse event.. 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.

The Phase 1/2 trial evaluating BOT/BAL in combination with FOLFOX and bevacizumab (“FOLFOX 3B”) in MSS mCRC was also presented at ASCO-GI in January 2025 and demonstrated promising efficacy, regardless of patients having liver metastases or not. Preliminary data show that the combination achieved a 71% ORR, with a 67% ORR specifically in patients with liver metastases. The regimen was well tolerated without dose limiting toxicities.

Based on these data, 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.

Clinical data sets in various tumor types including pancreas, lung, melanoma and sarcoma provide a path for additional expansion opportunities. Patients with advanced sarcomas face poor outcomes and have limited treatment options. In January 2025, data from the Phase 1 open label, multicenter study evaluating BOT/BAL combination across multiple sarcoma subtypes were published in the Journal of Clinical Oncology. Durable responses were observed across sarcoma types including visceral angiosarcoma, considered immunologically warm, and leiomyosarcoma, which are considered immunologically cold tumors. ORR was 19.2% for the overall study population (n=52). The ORR among angiosarcoma (n=18), visceral and cutaneous subtypes were 27.8%, 33.3% and 22.2% respectively. DCR was 65.4%, with a median PFS rate of 4.4 months. At a median follow-up of 9.1 months, median OS was not reached; the 12-month OS was 69%.

In addition to our lead clinical programs with botensilimab and the botensilimab/balstilimab combination, updated data from a Phase 1 clinical trial of AGEN2373 in combination with botensilimab in patients with advanced solid tumors was presented at the American Society of Clinical Oncology in June 2023. AGEN2373 showed single agent responses with no major toxicity. Responses were reported in patients with prostate cancer, ampullary carcinoma and metastatic vulvar squamous cell carcinoma. No hepatic toxicities, grade ≥3 treatment-related adverse events, or dose-limiting toxicities were observed at doses up to 10 mg/kg.

Our Strategy

Our strategy revolves around pioneering optimal combination treatments for cancer patients, with BOT as our cornerstone. Our immediate focus is the development of the BOT/BAL combination for the treatment of patients with CRC. As our data matures we will evaluate our regulatory strategy with the FDA and European Medicines Agency ("EMA") for the registration of the BOT/BAL combination treatment in CRC. We are focusing on externally funded trials for MSS CRC treatment settings.

In December 2024, we announced further detail to our strategic realignment to prioritize and focus resources to accelerate the development, registration, and commercialization of our BOT/BAL program where we have the greatest potential to benefit patients and to drive our future growth. Under this plan, we temporarily postponed all preclinical and clinical programs not related to BOT/BAL and reduced operating expenses across our global organization. We plan to expand combinations with BOT by integrating BAL and other complementary approaches within our clinical portfolio, leveraging targets like LAG-3, ILT2, and our CD137 agonist, AGEN2373. These innovations aim to mitigate disease and modulate the tumor microenvironment with a favorable tolerability profile. We drive portfolio advancement through a blend of independent development and strategic partnerships with industry leaders. Our overarching goal is to introduce innovative combination therapies that substantially enhance the patient population benefiting from current I-O treatments.

Our Antibody Discovery Platforms and Immunotherapy Programs

In addition to our clinical programs, our scientists have leveraged our 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. Some of these novel agents are advancing to the clinic via our pipeline or via partnering relationships. Given the diversity of our pipeline, we are well positioned to advance differentiated combination therapies with our goal to enhance response rates and expand the patient population that could benefit from innovative I-O combination treatments.

We possess end-to-end capabilities in-house – from discovery through to manufacturing – that have enabled us to advance our discoveries at lower costs with efficiency and speed. These product development advantages allow us 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 Sciences, Inc. (“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. 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. 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 July 2024, we received notice from BMS that it was voluntarily terminating the BMS License Agreement, effective as of January 26, 2025. Upon termination, BMS returned AGEN1777 to us.

Betta

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 the People’s Republic of China, Hong Kong, Macau and Taiwan (collectively, “Greater China”). 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.

Gilead

In December 2018, we entered into a series of agreements with Gilead to collaborate on the development and commercialization of up to five novel I-O therapies. Pursuant to the collaboration agreements, we received an upfront cash payment from Gilead of $120.0 million following the closing in January 2019. At closing, Gilead received worldwide exclusive rights to our bispecific antibody, AGEN1423, as well as a right of first negotiation for two undisclosed programs. Gilead also received the exclusive option to license exclusively AGEN1223, a bispecific antibody, and AGEN2373, a monospecific antibody. In November 2020, Gilead elected to return AGEN1423 to us and to voluntarily terminate the license agreement effective as of February 4, 2021. In the third quarter of 2021, we ceased development of AGEN1223 and in October 2021, the AGEN1223 option and license agreement was formally terminated. 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. 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. 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. Under the original collaboration agreement, programs targeting GITR, OX40 and two of the undisclosed targets were designated as profit-share programs, while the other targets were royalty-bearing programs. 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 at rates generally ranging from 6%-12%. 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 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. 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”). 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. In July 2024, Incyte announced that it would discontinue further development of the LAG-3 and TIM-3 monoclonal antibodies, and in February 2025, we received notice from Incyte formally terminating the collaboration effective February 2026, at which time Incyte will return to us all rights to LAG-3 and TIM-3.

Merck & Co.

In April 2014, we 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, a monospecific antibody targeting 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, triggering a $10.0 million milestone payment to us. Under the terms of the agreement, Merck is responsible for all future product development expenses for MK-4830, and we are eligible to receive potential milestone payments plus royalties on any future sales. 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.

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”). 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.

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 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”). 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 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 $136.3 million and $49.4 million and in potential development, regulatory, and commercial milestones from UroGen and Merck, respectively.

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. 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”). In addition to our lead clinical program, MiNK announced a collaboration with ImmunoScape, Inc. (“ImmunoScape”) to discover and develop next-generation T-cell receptor therapies against novel targets in solid tumors. MiNK will combine its unique, proprietary library of T cell antigens with ImmunoScape’s platform for rapid discovery of novel T cell receptors.

Founded in 2021, our subsidiary, SaponiQx, stands at the forefront of saponin-based adjuvant discovery and manufacturing. Its mission is to provide scalable and affordable vaccine adjuvants to enhance global health. SaponiQx is building an innovative adjuvant platform to deliver both sustainable manufacturing approaches and a secure supply of known adjuvants, as well as discover novel adjuvants and develop new, more effective vaccines utilizing optimized antigen-adjuvant pairings.

SaponiQx & QS-21 STIMULON Adjuvant

SaponiQx is our subsidiary that is building an integrated vaccine platform based on scalable and secure manufacturing of QS-21 STIMULON and other saponin-based adjuvants. 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 is a natural product, a triterpene glycoside, or saponin, purified from the bark of the Chilean soapbark tree, Quillaja, and 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 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 February 2024, SaponiQx and Ginkgo Bioworks, Inc. (“Ginkgo”) announced a 5-year contract totaling up to $31.0 million from the Department of Defense’s Defense Threat Reduction Agency (“DTRA”) to discover and develop next-generation vaccine 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 to optimize the plant cell culture process which we have developed for the purposes of scalable manufacturing cpcQS-21 and next-generation saponin-based adjuvants. In January 2019, we announced that the Bill & Melinda Gates Foundation awarded us a grant to develop the plant cell culture process for cpcQS-21 STIMULON. Our goal is to establish a platform for optimized and scalable vaccine adjuvant formulations to address pandemic threats and other disease settings. In 2023, SaponiQx announced a pivotal advancement in vaccine research and production with the availability of cGMP STIMULON cultured plant cell (“cpc”) QS-21. STIMULON cpcQS-21 is a sustainable and cost-efficient alternative to conventionally extracted QS-21 from bark extract, used in high-performance vaccines such as SHINGRIX and AREXVY.

In January 2025, SaponiQx entered into a strategic collaboration with Probius, a pioneer in quantum molecular spectroscopy for AI-driven discovery, and Ginkgo Bioworks. This partnership, fully funded by the DTRA Joint Science and Technology Office for the Chemical and Biological Defense Program, aims to accelerate the discovery and development of next-generation vaccine adjuvants to combat emerging viral, bacterial, and fungal threats. In August 2024, SaponiQx announced the availability of STIMULON cpcQS-21 on InvivoGen’s international retail infrastructure. SaponiQx’s STIMULON QS-21 is a key adjuvant component in market-leading vaccines for shingles, malaria, and respiratory syncytial virus. cpcQS-21 is derived from a cultured plant cell source, offering a sustainable alternative to conventional QS-21 extracted from a limited supply of tree bark. The latest preclinical data from cpcQS-21 was published in the journal Vaccines, in December 2024. 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). 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. GSK is obligated to supply us, or our affiliates, licensees, or customers, certain quantities of commercial grade QS-21 STIMULON for a stated period of time. In March 2012, we 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”). As consideration for entering into the GSK First Right to Negotiate Agreement, GSK paid us an upfront cash payment of $9.0 million, $2.5 million of which was creditable toward future royalty payments. We refer to the GSK License Agreement, the Amended GSK Supply Agreement and the GSK First Right to Negotiate Agreement collectively as the GSK Agreements. We are no longer entitled to any additional milestone payments under the GSK Agreements. 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. Notably, we have already monetized and sold this entire royalty stream as discussed in more detail below. The GSK License and Amended GSK Supply Agreements may be terminated by either party upon a material breach if the breach is not cured within the time specified in the respective agreement. The termination or expiration of the GSK License Agreement does not relieve either party from any obligation which accrued prior to the termination or expiration. Among other provisions, the license rights granted to GSK survive expiration of the GSK License Agreement. The license rights and payment obligations of GSK under the Amended GSK Supply Agreement survive termination or expiration, except that GSK’s license rights and future royalty obligations do not survive if we terminate due to GSK's material breach unless we elect otherwise. We do not incur clinical development costs for products partnered with GSK.

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. Under the terms of a note purchase agreement with the investor group (the “Note Purchase Agreement”), we received $100.0 million at closing for which the investors had the right to receive 100% of our worldwide royalties under the GSK License Agreement on sales of GSK’s Shingrix and malaria (“RTS,S”) prophylactic vaccine products that contain our QS-21 STIMULON adjuvant to pay down principle and interest. In November 2017, and pursuant to the Note Purchase Agreement, we received an additional $15.0 million in cash from the investors based on the approval of Shingrix by the FDA. Pursuant to the terms of this transaction, we retained the right to receive all royalties from GSK after all principal, interest and other obligations were satisfied under the Note Purchase Agreement. The Note Purchase Agreement also allowed us to buy back the loan and extinguish the notes early under pre-specified terms, which we did in January 2018.

In January 2018, we sold 100% of all royalties we were entitled to receive from GSK to Healthcare Royalty Partners III, L.P. and certain of its affiliates (“HCR”) and used the proceeds to extinguish the debt under the Note Purchase Agreement. HCR paid approximately $190.0 million at closing for the royalty rights, of which approximately $161.9 million was used to extinguish the prior notes, yielding us approximately $28.0 million in net proceeds. We were also entitled to receive up to $40.35 million in milestone payments from HCR based on sales of GSK’s vaccines as follows: (i) $15.1 million upon reaching $2.0 billion last-twelve-months net sales any time prior to 2024 (the “First HCR Milestone”) and (ii) $25.25 million upon reaching $2.75 billion last-twelve-months net sales any time prior to 2026 (the “Second HCR Milestone”). GSK’s net sales of Shingrix for the twelve months ended December 31, 2019, exceeded $2.0 billion. As a result, we received the First HCR Milestone of $15.1 million in 2020 after GSK’s net sales of Shingrix in 2019 exceeded $2.0 billion. GSK’s net sales of Shingrix for the twelve months ended June 30, 2022, exceeded $2.75 billion. As a result, we received the Second HCR Milestone of $25.25 million in 2022.

Manufacturing

Antibody Manufacturing

In December 2015, we acquired an antibody manufacturing pilot plant in Berkeley, California from XOMA Corporation (“XOMA”), which we refer to as “Agenus West.” A team of former XOMA employees with valuable chemistry, manufacturing and controls experience joined us and continue to operate the facility. Since the acquisition of Agenus West, we have made significant improvements in the plant, and added additional headcount increasing both scale and capacity. Agenus West is currently producing antibody drug substance for certain of our proprietary antibody programs (monospecific and bispecific). In some cases, we have been able to deliver clinical grade material from research cell banks in approximately six to nine months, which is significantly faster than the industry average of 12-18 months. Agenus West utilizes cutting-edge technology platforms, enabling us to be self-reliant and giving us the advantage of drug substance manufacturing speed, cost efficiency, operational flexibility and manufacturing technology transfer to commercial scale partners—all with desired product quality, and with the goal of benefiting patients. In November 2020, we entered into a long-term lease in Emeryville, CA for cGMP commercial manufacturing space. Construction of this end-to-end 83,000 square foot GMP clinical and commercial biologics manufacturing facility (from cell line development through Drug Product fill & finish, packaging and labeling) is complete and the facility is being commissioned for GMP manufacturing.

The quality control organization for all of our product candidates in Berkeley and Lexington, Massachusetts performs a series of release assays designed to ensure that our antibody drug substance meets all applicable specifications. Our quality assurance staff also reviews manufacturing and quality control records prior to batch release in an effort to assure conformance with cGMP as mandated by the FDA and foreign regulatory agencies. Our manufacturing staff is trained and routinely evaluated for conformance to rigorous manufacturing procedures and quality standards. This oversight is intended to ensure compliance with FDA and foreign regulations and to provide consistent drug substance output. Our quality control and quality assurance staff are similarly trained and evaluated as part of our effort to ensure consistency in the testing and release of the product, as well as consistency in materials, equipment and facilities.

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.