A Phase 2 Single Arm Trial of Stereotactic Body Radiation Therapy Followed by Dual Immune Checkpoint Inhibition for Patients With Metastatic Pancreatic Ductal Adenocarcinoma - The Miami "EMPIRE" Trial - Eradication of Metastatic Pancreatic Cancer With Immuno-Radiation

The purpose of this study is to assess if radiation therapy (which uses high-energy radiation to damage or destroy cancer cells) combined with immune checkpoint inhibitors (medications that helps the body recognize and attack cancer cells) will be beneficial for patients with metastatic pancreatic ductal adenocarcinoma.

Start Date01 Aug 2025

Sponsor / Collaborator

University of Miami

[+1]

NCT06782932

/ RecruitingPhase 1/2IIT

A Pilot Study Comparing Neoadjuvant and Adjuvant GVAX vs a Mutated KRAS Peptide Vaccine Given With Anti-PD-1 and Anti-CD137 for the Treatment of Surgically Resectable Pancreatic Adenocarcinoma

The purpose of this study is to determine the optimal dose of AGEN2373 that is safe when given in combination with balstilimab and Pancreatic GVAX Whole Cell Vaccine and evaluate the safety and clinical activity of balstilimab and AGEN2373 in combination with GVAX (Arm 1) or mKRASvax (Arm 2) in surgically resectable pancreatic adenocarcinoma.

Start Date27 May 2025

Sponsor / Collaborator

The Sidney Kimmel Comprehensive Cancer Center

[+3]

NCT06780787

/ RecruitingPhase 2IIT

Phase II Clinical Trial of FOLFOX, Botensilimab, Plus Balstilimab in Patients With Localized Rectal Cancer

This phase II trial tests how well fluorouracil, oxaliplatin and leucovorin calcium (folinic acid) (FOLFOX) with botensilimab and balstilimab given before surgery (neoadjuvant) works in treating patients with rectal adenocarcinoma that has not spread to other parts of the body (localized). Currently, neoadjuvant therapy for rectal cancer includes chemotherapy and chemoradiation. Despite these aggressive treatments, only about half of patients achieve a complete clinical response. In fact, over half of rectal cancer patients go on to have surgery and often suffer post-surgery complications involving urine and bowel problems. Thus, there has been an increased focus on non-surgical treatments. Chemotherapy drugs, such as fluorouracil, oxaliplatin and leucovorin calcium, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as botensilimab and balstilimab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Giving neoadjuvant FOLFOX with botensilimab and balstilimab may improve the rate of complete response and decrease the need for surgery and radiation therapy in patients with localized rectal adenocarcinoma.

Start Date20 May 2025

Sponsor / Collaborator

City of Hope National Medical Center

[+1]

100 Clinical Results associated with Balstilimab

100 Translational Medicine associated with Balstilimab

100 Patents (Medical) associated with Balstilimab

Literatures (Medical) associated with Balstilimab

10 Apr 2025·JOURNAL OF CLINICAL ONCOLOGY

Botensilimab (Fc-enhanced anti–cytotoxic lymphocyte-association protein-4 antibody) Plus Balstilimab (anti–PD-1 antibody) in Patients With Relapsed/Refractory Metastatic Sarcomas

Article

Author: Bullock, Andrea J. ; Jones, Robin L. ; Schwartz, Gary K. ; Grossman, Joseph E. ; Trent, Jonathan C. ; Johnson, Benny ; O'Day, Steven ; Avagyan, Manushak ; Agulnik, Mark ; Chand, Dhan ; Delepine, Chloe ; Henick, Brian ; Singh, Arun ; Gordon, Michael S. ; El-Khoueiry, Anthony B. ; Wu, Wei ; Stebbing, Justin ; Mahadevan, Daruka ; Wilky, Breelyn A. ; Tsimberidou, Apostolia M.

PURPOSE:

Outcomes for patients with advanced sarcomas are poor and there is a high unmet need to develop novel therapies. The purpose of this phase I study was to define the safety and efficacy of botensilimab (BOT), an Fc-enhanced anti–cytotoxic lymphocyte-association protein-4 antibody, plus balstilimab (BAL), an anti–PD-1 antibody, in advanced sarcomas.

METHODS:

BOT was administered intravenously (IV) at 1 mg/kg or 2 mg/kg once every 6 weeks in combination with BAL IV at 3 mg/kg once every 2 weeks for up to 2 years. The primary end point was to determine dose-limiting toxicities during the dose-escalation period. Secondary end points include objective response rate (ORR), duration of response (DOR), disease control rate, and progression-free survival (PFS) by RECIST 1.1. Exploratory end points include assessing patient biomarkers including tumor mutational burden, cytokines, and PD-L1 expression.

RESULTS:

Overall, 64 patients with sarcoma were treated; all were evaluable for safety and 52 for efficacy. The most common treatment-related adverse event (TRAE) was diarrhea/colitis occurring in 35.9% of patients, with grade 3 in 6.3% of patients. No grade 4 or 5 TRAEs were reported. For all evaluable patients, ORR was 19.2% (95% CI, 9.6 to 32.5), and 27.8% (95% CI, 9.7 to 53.5) for evaluable patients with angiosarcoma (n = 18); 33.3% in visceral and 22.2% in cutaneous subtypes. Median PFS for evaluable patients was 4.4 months (95% CI, 2.8 to 6.1), with a 6-month PFS rate of 36% (95% CI, 22 to 50) and a median DOR of 21.7 months (95% CI, 1.9 to not reached).

CONCLUSION:

The combination of BOT/BAL demonstrated promising efficacy and safety in a large cohort of heavily pretreated sarcoma patients. This encouraging activity warrants further investigation (ClinicalTrials.gov identifier: NCT03860272 ).

17 Feb 2025·CLINICAL CANCER RESEARCH

The Prostaglandin EP4 Antagonist Vorbipiprant Combined with PD-1 Blockade for Refractory Microsatellite-Stable Metastatic Colorectal Cancer: A Phase Ib/IIa Trial

Article

Author: Cristarella, Eleonora ; Niger, Monica ; Vitalini, Cristina ; Rovati, Lucio C. ; Chiodoni, Claudia ; Morano, Federica ; Zaffaroni, Nadia ; Brambilla, Nadia ; Doldi, Valentina ; Girolami, Federica ; Ghelardi, Filippo ; Giacovelli, Giampaolo ; Benincasa, Elena ; Pietrantonio, Filippo ; Palazzo, Michele ; Nichetti, Federico ; Sabella, Giovanna ; Manca, Paolo

Abstract:

Purpose::

Novel combinations are required to overcome resistance to immune checkpoint inhibitors in proficient mismatch repair (pMMR) or microsatellite-stable (MSS) metastatic colorectal cancer (mCRC). We aimed to determine whether vorbipiprant, a prostaglandin E2 receptor EP4 subtype antagonist, can convert immune-resistant mCRC into a tumor responsive to anti–PD-1 inhibition.

Patients and Methods::

This phase Ib/IIa prospective, open-label, single-arm trial followed a 3 + 3 dose-escalation and dose-optimization design. A total of 28 patients with chemorefractory pMMR/MSS mCRC were given dose-escalated oral vorbipiprant (30, 90, or 180 mg twice daily), along with biweekly intravenous balstilimab (3 mg/kg), an anti–PD-1 antibody. The primary endpoints included safety and the disease control rate (DCR). Secondary endpoints were the overall response rate, duration of response, progression-free survival, and overall survival.

Results::

No dose-limiting toxicities were observed. Of the 28 patients, seven (25%) experienced serious adverse events, but only one was attributed to vorbipiprant and one to balstilimab. The trial achieved a DCR of 50% observed across the entire cohort. In the subgroup of patients with liver metastases (n = 12), the DCR was 25%. The overall response rate was 11%, with three patients showing a partial response (median duration of response, 7.4 months). The median progression-free survival was 2.6 months, and the median overall survival was 14.2 months. Translational exploratory analyses suggested that vorbipiprant may boost response to anti–PD-1 in patients with immunogenic tumors.

Conclusions::

The combination of vorbipiprant and a PD-1 inhibitor (balstilimab) yielded sufficient activity in refractory pMMR/MSS mCRC, which is worthy of confirmation in future clinical trials in biomarker-enriched populations.

04 Nov 2024·NEURO-ONCOLOGY

Fc-enhanced anti-CTLA-4, anti-PD-1, doxorubicin, and ultrasound-mediated blood–brain barrier opening: A novel combinatorial immunotherapy regimen for gliomas

Article

Author: Kim, Kwang-Soo ; Najem, Hinda ; Horbinski, Craig ; Chand, Dhan ; Habashy, Karl ; Billingham, Leah ; Zhao, Junfei ; Lee-Chang, Catalina ; Huber, Olivia ; Butowski, Nicholas ; Muzzio, Miguel ; Saganty, Ruth ; Padney, Surya ; Miska, Jason ; Zhang, Bin ; Chen, Li ; Levey, Daniel ; Morin, Benjamin M ; Savitsky, David A ; Arrieta, Víctor A ; Dmello, Crismita ; Zhang, Daniel Y ; Heimberger, Amy B ; Hu, Jian ; Rabadan, Raul ; Castro, Brandyn ; Zhang, Peng ; Canney, Michael ; Phillips, Joanna J ; Gould, Andrew ; Stupp, Roger ; Amidei, Christina ; Marques, Marilyn ; Sonabend, Adam M

Abstract:

Background:

Glioblastoma is a highly aggressive brain cancer that is resistant to conventional immunotherapy strategies. Botensilimab, an Fc-enhanced anti-CTLA-4 antibody (FcE-aCTLA-4), has shown durable activity in “cold” and immunotherapy-refractory cancers.

Methods:

We evaluated the efficacy and immune microenvironment phenotype of a mouse analogue of FcE-aCTLA-4 in treatment-refractory preclinical models of glioblastoma, both as a monotherapy and in combination with doxorubicin delivered via low-intensity pulsed ultrasound and microbubbles (LIPU/MB). Additionally, we studied 4 glioblastoma patients treated with doxorubicin, anti-PD-1 with concomitant LIPU/MB to investigate the novel effect of doxorubicin modulating FcγR expressions in tumor-associated macrophages/microglia (TAMs).

Results:

FcE-aCTLA-4 demonstrated high-affinity binding to FcγRIV, the mouse ortholog of human FcγRIIIA, which was highly expressed in TAMs in human glioblastoma, most robustly at diagnosis. Notably, FcE-aCTLA-4-mediated selective depletion of intratumoral regulatory T cells (Tregs) via TAM-mediated phagocytosis, while sparing peripheral Tregs. Doxorubicin, a chemotherapeutic drug with immunomodulatory functions, was found to upregulate FcγRIIIA on TAMs in glioblastoma patients who received doxorubicin and anti-PD-1 with concomitant LIPU/MB. In murine models of immunotherapy-resistant gliomas, a combinatorial regimen of FcE-aCTLA-4, anti-PD-1, and doxorubicin with LIPU/MB, achieved a 90% cure rate, that was associated robust infiltration of activated CD8+ T cells and establishment of immunological memory as evidenced by rejection upon tumor rechallenge.

Conclusions:

Our findings demonstrate that FcE-aCTLA-4 promotes robust immunomodulatory and anti-tumor effects in murine gliomas and is significantly enhanced when combined with anti-PD-1, doxorubicin, and LIPU/MB. We are currently investigating this combinatory strategy in a clinical trial (clinicaltrials.gov NCT05864534).

142

News (Medical) associated with Balstilimab

29 Jul 2025

·www.prnewswire.com

Biotech Underdogs Line Up for Pivotal Shots at Game-Changing Cancer Treatments

Issued on behalf of Oncolytics Biotech Inc. VANCOUVER, B.C., July 29, 2025 /PRNewswire/ -- Equity Insider News Commentary – The average age of cancer patients is getting younger, as experts are urgently examining the rise of early-onset incidence across several different cancer types. According to the Cancer Discovery study from the National Cancer Institute (NCI), the largest increases were seen in female breast, colorectal, kidney, uterine, and pancreatic cancers. Biotechs in the oncology space are responding with optimistic new treatments with potential milestones in the near future that may shift the tide in the sector, including Oncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC), Celcuity Inc. (NASDAQ: CELC), Evaxion A/S (NASDAQ: EVAX), Lyell Immunopharma, Inc. (NASDAQ: LYEL), and Agenus Inc. (NASDAQ: AGEN). Globally, the cancer‑drug sector is projected to surpass US$900billion in sales by 2034, according to Vision Research Reports. Next‑generation therapeutics (those powered by precision and personalized medicine) are pegged by Precedence Research to hit US$175.2billion during that same time period, growing at a 7.35% CAGR. Oncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC) has officially entered the most critical phase of its journey yet—pursuing a potential registration-enabled trial in first-line metastatic pancreatic ductal adenocarcinoma (mPDAC), for its flagship asset, pelareorep. The company announced it has begun formal discussions with the U.S. Food and Drug Administration (FDA) aimed at finalizing a pivotal study design, with trial start-up activities expected to begin before the end of 2025. For investors and potential partners, this marks a clear shift from promising data to regulatory execution in one of the deadliest solid tumors in medicine. "We expect to move quickly and decisively down a clear regulatory path," said Jared Kelly, CEO of Oncolytics. "This is about execution and focus. Our goal is to win on survival—and this pivotal study is how we do it. We believe this program not only creates significant value for shareholders but also positions Oncolytics as a highly attractive partner for pharma companies seeking to break open the immunotherapy landscape in mPDAC and other GI tumors." The move comes as Oncolytics sharpens its focus on pelareorep, a systemically delivered oncolytic virus designed to convert so-called "cold" tumors—those that are typically invisible to the immune system—into "hot" tumors that can respond to immunotherapy. Pelareorep has been studied across over 1,100 patients and has demonstrated promising results in difficult cancers like mPDAC and HR+/HER2- breast cancer, particularly when used in combination with chemotherapy and immune checkpoint inhibitors. In first-line pancreatic cancer, pelareorep-based regimens have shown a notable 21.9% two-year overall survival rate, compared to a 9.2% historical benchmark. In a separate study pairing pelareorep with chemotherapy and a checkpoint inhibitor, researchers recorded a 62% objective response rate—remarkable given that checkpoint inhibitors are not currently approved for use in this indication. This robust efficacy signal, along with impressive translational data, helped lay the groundwork for this regulatory step. "This robust data set, amassed from several studies in cancers that have historically resisted immunotherapeutic approaches, provides definitive validation of pelareorep's immune-mediated mechanism of action," said Dr. Thomas Heineman, Chief Medical Officer of Oncolytics. "We observed tumor biopsy-confirmed virus replication, immune cell activation, and the recruitment of cytotoxic T cells into the TME – all consistent with the durable responses observed in patients with metastatic PDAC and HR+/HER2- breast cancer who were treated with pelareorep." Earlier this month, Oncolytics hosted a key opinion leader event featuring gastrointestinal cancer experts who reviewed survival outcomes, biomarker validation, and the drug's potential role in combination therapy. That expert panel helped reinforce the view that pelareorep's mechanism—activating innate and adaptive immune responses in patients—is both biologically sound and commercially relevant. Oncolytics' execution-focused strategy is being led by Jared Kelly and Andrew Aromando, who both played key roles in Ambrx Biopharma's US$2 billion acquisition by Johnson & Johnson. Kelly was appointed CEO earlier this year, while Aromando recently joined as Chief Business Officer. Together, along with Oncolytics' already-established team, they're guiding the company into late-stage development with a sharp focus on capital efficiency and strategic alignment. Regulatory designations are already in place to accelerate development. Pelareorep holds Fast Track and Orphan Drug designations for pancreatic cancer (and Fast Track for HR+/HER2‑ mBC breast cancer) from the FDA, meaning the agency has already recognized both the drug's potential and the serious unmet need in this patient population. These statuses not only streamline review processes but also increase the attractiveness of the program to potential pharmaceutical partners. For context, pancreatic cancer is one of the deadliest common cancers, with a five-year survival rate of less than 14%. Most patients are diagnosed at a metastatic stage, and current treatment options provide limited benefit. Unlike other cancers where immunotherapies like checkpoint inhibitors have transformed care, mPDAC remains largely resistant to those approaches—making the promise of pelareorep especially notable. What distinguishes pelareorep is its dual capability: it acts as both a viral therapy that replicates in cancer cells and a biological agent that activates the body's own immune response. Tumor samples have shown increased PD-L1 expression, heightened interferon signaling, and infiltration of tumor-killing T cells—all hallmark indicators that the immune system is being mobilized against cancer. These features are seen as essential for the next generation of immuno-oncology approaches. With this latest milestone, Oncolytics is entering a phase where the outcomes of FDA interaction will shape not only clinical plans but also potential commercial partnerships. If the agency accepts the company's proposed trial framework and endpoints—centered around overall survival—the resulting study could become the definitive test for pelareorep's market potential in mPDAC. More details on the trial design and timing are expected once FDA feedback is received, but the goal is clear: initiate the pivotal trial start-up activities before the end of 2025 and establish pelareorep as a cornerstone immunotherapy in one of the most underserved cancer settings. In the meantime, the company remains active in its ongoing breast cancer program and is continuing to explore pelareorep's potential in other gastrointestinal cancers, including KRAS-mutated colorectal cancer. However, first-line pancreatic cancer has now emerged as the lead strategic focus. The transition from early-stage promise to registration-stage planning marks a decisive evolution in the Oncolytics story. With data in hand, regulatory engagement underway, and a seasoned leadership team at the helm, Oncolytics is advancing into its most consequential chapter yet. CONTINUED… Read this and more news for Oncolytics Biotech at: In other recent industry developments and happenings in the market include: Celcuity Inc. (NASDAQ: CELC) recently announced that its Phase 3 VIKTORIA-1 trial met both progression-free survival (PFS) primary endpoints in patients with HR+/HER2- breast cancer without PIK3CA mutations. Gedatolisib-based combinations showed significant PFS improvements compared to standard therapies, including a 7.3-month gain for the triplet arm (9.3 vs. 2.0 months for fulvestrant monotherapy) and a 5.4-month gain for the doublet (7.4 vs. 2.0 months for fulvestrant monotherapy). "The efficacy improvement relative to the control that each of the gedatolisib regimens demonstrated was historic for this patient population," said Brian Sullivan, Chairman, CEO and co-founder of Celcuity. "We are excited about the potential opportunity to provide a breakthrough therapeutic option for patients with HR-positive, HER2-negative, PIK3CA wild-type advanced breast cancer." The company plans to discuss a potential NDA submission with the FDA following a full data presentation later this year. Lyell Immunopharma, Inc. (NASDAQ: LYEL) announced impressive new data from its LYL314 trial in relapsed/refractory large B-cell lymphoma, showing an 88% overall response rate and 72% complete response rate in the 3L+ setting. Over 70% of complete responders remained disease-free at 6 months. "Based on these robust data, and our recent End-of-Phase 1 meeting with the FDA, we have initiated PiNACLE, a single-arm pivotal trial of LYL314 in patients with large B-cell lymphoma in the third- or later-line setting and remain on track to initiate a pivotal trial to evaluate LYL314 in the second-line setting by the beginning of 2026," said Lynn Seely, MD, President and CEO of Lyell. The pivotal PiNACLE trial is now underway to support potential approval of this next-generation dual-targeting CAR T therapy. Later this year in October, Evaxion A/S (NASDAQ: EVAX) shared it will be presenting two-year data at ESMO 2025 from its Phase 2 trial of EVX-01, an AI-designed personalized cancer vaccine, showing durable responses in advanced melanoma. Results included a 69% overall response rate and a strong correlation between AI predictions and immune activity. The study supports EVX-01's role as a first-line immunotherapy candidate when paired with checkpoint inhibitors like pembrolizumab. "We are delighted to have the two-year data from the EVX-01 phase 2 trial accepted for presentation at the ESMO Congress 2025," said Birgitte Rønø, CSO and interim CEO of Evaxion. "As one of the most important and prestigious medical oncology conferences in the world, the congress will be a great place for us to present the data to a large audience, including potential partners." Also at ESMO 2025, Agenus Inc. (NASDAQ: AGEN) will present survival data from its botensilimab/balstilimab program, including an oral session highlighting survival plateaus across five refractory tumor types. With over 1,200 patients treated, the agents are showing promising results in historically cold tumors like mCRC and non-melanoma skin cancer. These data continue to support botensilimab as a backbone immunotherapy candidate for solid tumors. Source: CONTACT: Equity Insider [email protected] (604) 265-2873 DISCLAIMER: Nothing in this publication should be considered as personalized financial advice. We are not licensed under securities laws to address your particular financial situation. No communication by our employees to you should be deemed as personalized financial advice. Please consult a licensed financial advisor before making any investment decision. This is a paid advertisement and is neither an offer nor recommendation to buy or sell any security. We hold no investment licenses and are thus neither licensed nor qualified to provide investment advice. The content in this report or email is not provided to any individual with a view toward their individual circumstances. Equity Insider is a wholly-owned subsidiary of Market IQ Media Group, Inc. ("MIQ"). MIQ has been paid a fee for Oncolytics Biotech Inc. advertising and digital media from the company directly. There may be 3rd parties who may have shares of Oncolytics Biotech Inc., and may liquidate their shares which could have a negative effect on the price of the stock. This compensation constitutes a conflict of interest as to our ability to remain objective in our communication regarding the profiled company. Because of this conflict, individuals are strongly encouraged to not use this publication as the basis for any investment decision. The owner/operator of MIQ own shares of Oncolytics Biotech Inc. which were purchased in the open market, and reserve the right to buy and sell, and will buy and sell shares of Oncolytics Biotech Inc. at any time without any further notice commencing immediately and ongoing. We also expect further compensation as an ongoing digital media effort to increase visibility for the company, no further notice will be given, but let this disclaimer serve as notice that all material, including this article, which is disseminated by MIQ has been approved by Oncolytics Biotech Inc.; this is a paid advertisement, we currently own shares of Oncolytics Biotech Inc. and will buy and sell shares of the company in the open market, or through private placements, and/or other investment vehicles. While all information is believed to be reliable, it is not guaranteed by us to be accurate. Individuals should assume that all information contained in our newsletter is not trustworthy unless verified by their own independent research. Also, because events and circumstances frequently do not occur as expected, there will likely be differences between the any predictions and actual results. Always consult a licensed investment professional before making any investment decision. Be extremely careful, investing in securities carries a high degree of risk; you may likely lose some or all of the investment. Logo - SOURCE Equity Insider WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Clinical ResultImmunotherapyPhase 2Fast TrackOrphan Drug

25 Jul 2025

·www.businesswire.com

Agenus to Highlight Emerging Survival Plateaus with Botensilimab/Balstilimab in Oral Presentation of Study in Refractory Patients Across Five Tumor Types at ESMO 2025

LEXINGTON, Mass.--(BUSINESS WIRE)--Agenus Inc. (Nasdaq: AGEN), a leader in immuno-oncology, today announced that four abstracts highlighting clinical progress across its botensilimab and balstilimab immunotherapy programs have been accepted for presentation at the European Society for Medical Oncology (ESMO) Congress 2025, taking place in Berlin, Germany from October 17-21. The highlight is an oral presentation that will feature emerging survival plateaus from a study of botensilimab plus balstilimab in 343 evaluable patients with refractory metastatic solid tumors across five tumor types. Three additional poster presentations will feature data from investigator-sponsored studies in cervical cancer, MSS metastatic colorectal cancer (mCRC), and non-melanoma skin cancers, underscoring the broad potential of botensilimab and balstilimab based combinations in difficult-to-treat cancers. Presentation Details: Dr. Michael Gordon; HonorHealth Research Institute-AZ, USA Mini Oral Session: Investigational Immunotherapy Session Date: Friday, October 17, 2025 Session Time: 2:00-3:00 PM CEST / 8:00-9:30 AM EDT Location: Hall 5.2 Abstract Number: 3220 2. Session Date: Saturday, October 18, 2025 Session Time: 12:00-12:45 PM CEST / 6:00-6:45 AM EDT Location: Hall 25 Abstract Number: 2952 Poster Number: 1164P 3. Presenting Author: Dr. Marwan Fakih; City of Hope- CA, USA Session Date: Sunday, October 19, 2025 Session Time: 12:00-12:45 PM CEST / 6:00-6:45 AM EDT Location: Hall 25 Abstract Number: 6197 Poster Number: 851P 4. Presenting Author: Dr. Iwona Lugowska; Maria Sklodowska-Curie National Research Institute and Oncology Center - Poland Session Date: Monday, October 20, 2025 Session Time: 12:00-12:45 PM CEST / 6:00-6:45 AM EDT Location: Hall 25 Abstract Number: 7273 Poster Number: 1662P About Agenus Agenus is a leading immuno-oncology company targeting cancer with a comprehensive pipeline of immunological agents. The company was founded in 1994 with a mission to expand patient populations benefiting from cancer immunotherapy through combination approaches, using a broad repertoire of antibody therapeutics, adoptive cell therapies (through MiNK Therapeutics) and adjuvants (through SaponiQx). Agenus has robust end-to-end development capabilities, across commercial and clinical cGMP manufacturing facilities, research and discovery, and a global clinical operations footprint. Agenus is headquartered in Lexington, MA. For more information, visit www.agenusbio.com or @agenus_bio. Information that may be important to investors will be routinely posted on our website and social media channels. About Botensilimab (BOT) Botensilimab is a multifunctional, human Fc enhanced CTLA-4 blocking antibody designed to boost both innate and adaptive anti-tumor immune responses. Its novel design leverages mechanisms of action to extend immunotherapy benefits to “cold” tumors which generally respond poorly to standard of care or are refractory to conventional PD-1/CTLA-4 therapies and investigational therapies. Botensilimab augments immune responses across a wide range of tumor types by priming and activating T cells, downregulating intratumoral regulatory T cells, activating myeloid cells and inducing long-term memory responses. Botensilimab alone, or in combination with Agenus’ investigational PD-1 antibody, balstilimab, has shown clinical responses across nine metastatic, late-line cancers. Approximately 1,200 patients have been treated across the botensilimab/balstilimab program in phase 1 and phase 2 clinical trials. For more information about botensilimab trials, visit www.clinicaltrials.gov. About Balstilimab (BAL) Balstilimab is a novel, fully human monoclonal immunoglobulin G4 (IgG4) designed to block PD-1 (programmed cell death protein 1) from interacting with its ligands PD-L1 and PD-L2. It has been evaluated in >900 patients to date and has demonstrated clinical activity and a favorable tolerability profile in several tumor types. Forward-Looking Statements This press release contains forward-looking statements that are made pursuant to the safe harbor provisions of the federal securities laws, including statements regarding its botensilimab and balstilimab programs, expected regulatory timelines and filings, and any other statements containing the words "may," "believes," "expects," "anticipates," "hopes," "intends," "plans," "forecasts," "estimates," "will," “establish,” “potential,” “superiority,” “best in class,” and similar expressions are intended to identify forward-looking statements. These forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially. These risks and uncertainties include, among others, the factors described under the Risk Factors section of our most recent Annual Report on Form 10-K for 2024, and subsequent Quarterly Reports on Form 10-Q filed with the Securities and Exchange Commission. Agenus cautions investors not to place considerable reliance on the forward-looking statements contained in this release. These statements speak only as of the date of this press release, and Agenus undertakes no obligation to update or revise the statements, other than to the extent required by law. All forward-looking statements are expressly qualified in their entirety by this cautionary statement.

ImmunotherapyPhase 2Phase 1

07 Jul 2025

·pipelinereview.com

Agenus’ BOT/BAL Achieves 42% Two-Year Survival in Refractory MSS CRC, Advances Toward Registration with FDA Alignment on Phase 3

LEXINGTON, MA, USA I July 07, 2025 I Agenus Inc. (Nasdaq: AGEN) a leader in immuno-oncology innovation, today announced that its botensilimab and balstilimab (BOT/BAL) combination achieved a two-year survival rate of 42% along with a now more mature 21-month median overall survival (OS) in an expanded cohort of 123 patients with microsatellite-stable (MSS) metastatic colorectal cancer (mCRC) without active liver metastases (NLM). Agenus also confirmed that it has reached agreement with the U.S. Food and Drug Administration (FDA) on the design of the global BATTMAN Phase 3 trial. The FDA waived the need for a BOT monotherapy arm, allowing for a simple two-arm study design. These new BOT/BAL data were reported at the 2025 ESMO Gastrointestinal Cancers Congress (ESMO-GI) in Barcelona, Spain, along with regulatory updates from its July 1, 2025 End-of-Phase 2 (EoP2) meeting with the U.S. Food and Drug Administration (FDA). “Deep, durable responses and survival plateaus emerging at two years and beyond are rarely seen in microsatellite stable refractory colorectal cancer …” said Dr. Steven O’Day, Chief Medical Officer at Agenus. Share ESMO‑GI Clinical Highlights The new data presented at ESMO-GI represent an approximate 40% increase in number of patients (n=123) compared to earlier reports published in Nature Medicine in 2024. The expanded dataset demonstrates continued durability of tumor responses and median overall survival approaching two years in an immunotherapy-resistant treatment setting. Among these 123 heavily pretreated MSS mCRC patients (third-line or later) treated with BOT/BAL, the confirmed objective response rate (ORR) was 20%, with a median duration of response (DOR) of 16.6 months. The disease control rate (DCR, responses plus stable disease) was 69%. Notably, median overall survival (OS) reached 20.9 months, with 42% of patients still alive at two years in this refractory population. Patients in fourth-line or later (n=37), having exhausted all standard therapies, saw similar benefits, with a ~19% ORR and 43% two-year survival. These findings are particularly meaningful in this refractory population for which best supportive care has been historically limited to roughly 5-8 months median overall survival. No new safety signals were observed. Immune-related side effects were manageable and no treatment-related deaths occurred. The combination was tolerated across dose levels. “These results reinforce the consistency and durability of the botensilimab plus balstilimab combination in a population that has historically seen minimal benefit from immune checkpoint blockade,” said Dr. Benjamin Schlechter of Dana-Farber Cancer Institute , who presented the data. “For patients with MSS colorectal cancer who have exhausted standard therapies, this combination is showing the kind of meaningful, long-lasting benefit we rarely see in this setting. It has the potential to fundamentally shift how we treat this disease.” “Deep, durable responses and survival plateaus emerging at two years and beyond are rarely seen in microsatellite stable refractory colorectal cancer – they are usually only seen in highly immunogenic tumors,” said Dr. Steven O’Day, Chief Medical Officer of Agenus. “These data reinforce the potential for a chemo‑free option in a population with limited alternatives.” FDA Meeting Outcomes Official minutes from the July 1, 2025 End-of-Phase 2 (EoP2) meeting reflect a meaningful shift in FDA alignment since July 2024, establishing two new areas of agreement: During the discussion on July 1, 2025, the FDA stated that it continues to recommend Agenus conduct a randomized controlled trial to support the approval of BOT/BAL in the metastatic setting and the demonstrated magnitude of treatment effect “does not appear to meet the standard of reasonably likely to predict benefit.” Agenus and key experts in oncology and immunotherapy, including those present in the FDA meeting—strongly believe that the BOT/BAL data meets the standard of Subpart E given the magnitude, durability, and urgent unmet need in this patient population. Jennifer Buell, Ph.D., Executive Chairwoman of Agenus, commented: “FDA’s acknowledgement of balstilimab’s role and its constructive guidance on the Phase 3 trial mark a pivotal step forward. We have incorporated the Agency’s input and are moving swiftly to launch BATTMAN, while continuing to mature our existing dataset. Guided by Commissioner Makary’s commitment to accelerate promising therapies, we intend to use every expedited pathway—Fast Track, Real-Time Oncology Review, the new Commissioner’s National Priority Voucher Program, and other accelerated mechanisms—to bring this chemo-free option to patients who have exhausted all other treatments.” Clinical Urgency “Colorectal cancer is rising fastest in people under 50 and is projected to become the leading cause of cancer death in that age group by 2030,” said Richard Goldberg, M.D., Chief Development Officer, Agenus. “Given the dismal five‑to‑eight‑month median survival with current late‑line therapies, making BOT/BAL available quickly is not just prudent—it is imperative.” 2H2025 Catalysts Agenus’ Commitment to Patient Access Agenus is committed to making our investigational medicines available to patients with cancer. Our goal is to provide access to our investigational medicines at the appropriate time and in the correct manner for patients. You can find information on access on our website at www.agenusbio.com/medical-affairs/ and apply. About the C-800-01 Phase 1 Study The C-800-01 Phase 1, open-label, multicenter trial (NCT03860272) evaluated botensilimab alone or in combination with balstilimab across multiple solid tumors, including an expansion cohort in microsatellite stable metastatic colorectal cancer. In the MSS CRC cohort, patients received botensilimab (1 or 2 mg/kg every six weeks) plus balstilimab (3 mg/kg every two weeks) for up to two years. The study enrolled heavily pretreated patients, including those with no active liver metastases, and assessed safety, objective response rate, progression-free survival, and overall survival. No maximum tolerated dose was reached, and the safety profile was manageable across dose levels. The trial also included exploratory biomarker analyses to inform potential predictors of response. Preliminary findings from this study in refractory MSS CRC were published in Nature Medicine in September 2024. About Agenus Agenus is a leading immuno-oncology company targeting cancer with a comprehensive pipeline of immune-driven therapies. Founded in 1994, the company’s mission is to expand the patient populations benefiting from cancer immunotherapy through innovative combination approaches. Agenus’ portfolio includes a broad repertoire of antibody therapeutics, adoptive cell therapies (via its affiliate MiNK Therapeutics), and adjuvants (via SaponiQx). The company has end-to-end capabilities spanning research, discovery, and GMP manufacturing, and it has a global clinical development footprint. Agenus is headquartered in Lexington, MA. For more information, visit www.agenusbio.com or follow @agenus_bio on social media. Important information for investors will be routinely posted on the company’s website and social channels. About Botensilimab (BOT) Botensilimab (AGEN1181) is a novel, multifunctional, Fc-enhanced CTLA-4 antibody engineered to boost both innate and adaptive anti-tumor immune responses. Its unique design aims to overcome the limitations of first-generation CTLA-4 inhibitors (like ipilimumab) and extend immunotherapy benefits to “cold” tumors that typically respond poorly or not at all to standard immune checkpoint blockade. Botensilimab’s Fc-enhanced structure allows it to robustly engage activating Fc receptors on key immune cells, thereby priming and activating T cells, depleting immunosuppressive regulatory T cells in the tumor microenvironment, activating myeloid cells, and inducing long-term immune memory. Through these mechanisms, botensilimab has demonstrated the ability to ignite immune responses across a range of solid tumors, including those resistant to conventional PD-1 or CTLA-4 therapies. To date, approximately 1,200 patients have been treated with botensilimab and/or balstilimab in Phase 1 and 2 trials. Botensilimab alone or in combination with Agenus’ investigational PD-1 antibody balstilimab has shown clinical responses in nine different metastatic cancers in late-line settings. For more information on ongoing botensilimab trials, please visit www.clinicaltrials.gov . About Balstilimab (BAL) Balstilimab (AGEN2034) is a novel, fully human monoclonal IgG4 antibody that blocks PD-1 (programmed cell death-1) from interacting with its ligands PD-L1 and PD-L2. By inhibiting the PD-1 checkpoint pathway, balstilimab aims to restore T-cell activity against tumors. It has been evaluated in over 900 patients to date and has demonstrated clinical activity with a favorable tolerability profile in several tumor types. Balstilimab is being studied both as a monotherapy and in combination with other agents (such as botensilimab) to expand its therapeutic impact. SOURCE: Agenus

Clinical ResultImmunotherapyPhase 3Phase 1

100 Deals associated with Balstilimab

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KEGG	Wiki	ATC	Drug Bank
D11820	-	-	DB15676

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Uterine Cervical Cancer	NDA/BLA	United States	Recepta Biopharma SA	30 Jan 2022
Liver metastases	Phase 3	France	Agenus, Inc.	15 Oct 2024
Metastatic gastric adenocarcinoma	Phase 3	France	Agenus, Inc.	15 Oct 2024
Anus Neoplasms	Phase 3	Netherlands	Agenus, Inc.	29 Jan 2024
Esophageal Squamous Cell Carcinoma	Phase 3	Netherlands	Agenus, Inc.	29 Jan 2024
Mismatch repair-deficient Solid Tumors	Phase 3	Netherlands	Agenus, Inc.	29 Jan 2024
Advanced cancer	Phase 3	United States	Agenus, Inc.	02 Aug 2021
Advanced cancer	Phase 3	Armenia	Agenus, Inc.	02 Aug 2021
Metastatic Carcinoma to the Uterine Cervix	Phase 3	United States	Agenus, Inc.	02 Aug 2021
Metastatic Carcinoma to the Uterine Cervix	Phase 3	Armenia	Agenus, Inc.	02 Aug 2021

Clinical Result

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Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03104699 (Phase 2 study \| Phase I dose escalation, CTgov)	Phase 1/2	Locally Advanced Malignant Solid Neoplasm \| Recurrent Cervical Cancer \| Metastatic Carcinoma to the Uterine Cervix ... View more	211	Balstilimab (Phase 1: Balstilimab Dose 1)	iwalckzcxt = pqgahwgkyt vopfuhvfkn (xfcglcddrw, quhdrpyytc - kvtlvzstiq) View more	-	30 Jul 2025
				Balstilimab (Phase 1: Balstilimab Dose 2)	iwalckzcxt = oskgzitdmk vopfuhvfkn (xfcglcddrw, yceiygdmyq - rhmgavzrur) View more
NCT03860272 (Pubmed \| J Clin Oncol) Manual	Phase 1	Sarcoma	64	Botensilimab + Balstilimab	acceccatqz(gjrlrcoere) = The most common treatment-related adverse event (TRAE) was diarrhea/colitis occurring in 35.9% of patients, with grade 3 in 6.3% of patients. mnpmzgurrm (lhysodjjte )	Positive	27 Jan 2025
				Botensilimab + Balstilimab (angiosarcoma)
UNICORN (ASCO_GI2025)	Phase 2	Mismatch repair-deficient Colonic Cancer Neoadjuvant pMMR \| dMMR	56	Botensilimab 1 mg/kg	jviwugjwdi(ghiivligrv) = bsbvcrblal tmphbedmsr (swpunbxuxi ) View more	Positive	23 Jan 2025
				Botensilimab 1 mg/kg + Balstilimab 3 mg/kg	ifhcjilqlg(gsmutqjncc) = roznnycgys ubpttjnadd (xdtabpozeo ) View more
NCT05608044 (ASCO_GI2025)	Phase 2	Metastatic Microsatellite Stable Colorectal Carcinoma MSS \| pMMR \| KRAS mutant ... View more	234	Botensilimab 75 mg Q6W	lfgvxwphwg(ntponevvkf) = vuesqyafyi linivpbidw (fpwygplnlc ) View more	Positive	23 Jan 2025
				Botensilimab 150 mg Q6W	lfgvxwphwg(ntponevvkf) = nimmmtnnhl linivpbidw (fpwygplnlc ) View more
NCT05627635 (ASCO_GI2025)	Phase 1	Microsatellite Stable Colorectal Carcinoma MSS	14	Folinic acid, fluorouracil, oxaliplatin, bevacizumab, botensilimab, balstilimab (FOLFOX-3B)	jgsapkqfgv(iufyopsumt) = one pt at DL1 with transient G3 AST/ALT elevation and transient G2 colitis (resolved with steroids and infliximab), one pt at DL1 with G2 hypothyroidism and one patient at DL2 with G2 hyperthyroidism zacabeysaz (zcwmfddrjo ) View more	Positive	23 Jan 2025
NCT05864534 (Pubmed \| Neuro Oncol)	Phase 2	Glioma	-	FcE-aCTLA-4	goukysdgxz(qskzueuaxk) = mghsefqmaw damanozfjs (nblyhksewm )	-	04 Nov 2024
NCT03860272 (ESMO2024) Manual	Phase 1	Sarcoma	63	Botensilimab balstilimab	silbmisitk(hzundtcdwt) = Any grade immune-mediated adverse events (AEs) occurred in 52% of pts, most commonly, diarrhea/colitis (38%; 11% Gr3). No Gr4 or 5 treatment-related AEs occurred. rpweyritiq (morqxcharx ) View more	Positive	13 Sep 2024
NCT03860272 (NEST-1, Biospace) Manual	Phase 1/2	Colonic Cancer Neoadjuvant Microsatellite Stable (MSS) \| MSI-High	20	botensilimab with balstilimab + botensilimabal dosbalstilimablimab (MSS + NEST-1 cohort)	ymldchliuk(vesgzhcluh) = pxnszuenhv dqzjnjjntp (hsadnjzllf ) View more	Positive	28 Jul 2024
				botensilimab with balstbalstilimab + botensilimabal dose of balstilimab (MSI-H + NEST-1 cohort)	ymldchliuk(vesgzhcluh) = zvybslvnwl dqzjnjjntp (hsadnjzllf ) View more
NCT05608044 (BusinessWire) Manual	Phase 2	Metastatic Microsatellite Stable Colorectal Carcinoma	-	Botensilimab 75mg + Balstilimab 240mg	yvekftxgts(wkfengjqda) = ukttztnlcx bejwmayxgl (hxshsfnhqd, 10.4 - 31.4) View more	Positive	18 Jul 2024
				Botensilimab 150mg + Balstilimab 240mg	yvekftxgts(wkfengjqda) = ycakxuiqhz bejwmayxgl (hxshsfnhqd, 2.7 - 18.1)
NCT05205330 (ASCO2024) Manual	Phase 1/2	Metastatic Microsatellite Stable Colorectal Carcinoma pMMR/MSS	-	Vorbipiprant 30balstilimab	rssfrkxamx(tqtmekdrzf) = qowqwwdqkw aukwkzdyak (jyciljleec ) View more	Positive	24 May 2024
				Vorbipiprant 90balstilimab	rssfrkxamx(tqtmekdrzf) = bcmfjbuvql aukwkzdyak (jyciljleec ) View more

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