{"success":true,"data":{"pressRelease":{"id":"128381","rtpr_id":"nBwcb1GgYa","ticker":"AGEN","exchange":"NASDAQ","all_tickers":["AGEN"],"title":"Agenus Announces Updated NEST Phase 2 Publication Reporting Deep Pathologic Responses and No Observed Recurrences with Neoadjuvant BOT+BAL in Resectable Colon Cancer","author":"Business Wire","published_at":"2026-08-26T14:05:00.098Z","article_body":"Agenus Announces Updated NEST Phase 2 Publication Reporting Deep Pathologic\nResponses and No Observed Recurrences with Neoadjuvant BOT+BAL in Resectable\nColon Cancer\n\n\n * No colorectal cancer recurrences observed at updated median follow-up of 32.2\nmonths in NEST-1 and 23.5 months in NEST-2\n\n * In pMMR/MSS tumors, neoadjuvant BOT+BAL achieved 59% pathologic response,\nincluding 41% major pathologic response and 32% pathologic complete response\n\n * 88% of evaluable patients cleared ctDNA before surgery, with no delays to\nplanned surgical resection\n\n * Longer follow-up and immune analysis provide clinical and biological support\nfor Agenus’ planned global Phase 3 ROBBIN trial in curative-intent MSS/pMMR\ncolon cancer\n\nAgenus\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=http%3A%2F%2Fwww.agenusbio.com&esheet=54594588&newsitemid=20260826183640&lan=en-US&anchor=Agenus&index=1&md5=7dc2a3fc88e094e49d5320b5df32e498)\nInc. (Nasdaq: AGEN), a leader in immuno-oncology innovation, today announced\nthe peer-reviewed publication of updated results from the\ninvestigator-sponsored Phase 2 NEST trial evaluating neoadjuvant botensilimab\n(BOT), Agenus’ multifunctional, Fc-enhanced anti-CTLA-4 antibody, and\nbalstilimab (BAL), Agenus’ anti-PD-1 antibody, in patients with resectable\ncolon cancer. The manuscript, titled “Neoadjuvant botensilimab/balstilimab\nfor localized mismatch repair proficient and deficient colon cancer: Results\nof the NEST phase 2 clinical trial,” was published in Clinical Cancer\nResearch and is available here\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Faacrjournals.org%2Fclincancerres%2Farticle%2Fdoi%2F10.1158%2F1078-0432.CCR-26-0998%2F787654%2FNeoadjuvant-Botensilimab-Balstilimab-for-localized&esheet=54594588&newsitemid=20260826183640&lan=en-US&anchor=here&index=2&md5=65ad473756164432fd3df2f6a439dbb3)\n.\n\nEarlier findings from NEST were presented at the 2025 ASCO Gastrointestinal\nCancers Symposium. The publication provides longer follow-up and a fuller\npeer-reviewed analysis of tumor responses, circulating tumor DNA (ctDNA)\ndynamics, disease-free follow-up and immune changes in the tumor\nmicroenvironment.\n\nAt the March 31, 2026 data cutoff, no colorectal cancer recurrences had been\nobserved, with median follow-up of 32.2 months in NEST-1 and 23.5 months in\nNEST-2. Among 22 mismatch repair proficient/microsatellite stable (pMMR/MSS)\ntumors, 59% achieved a pathologic response, including 41% with a major\npathologic response and 32% with a pathologic complete response.\n\nMSS/pMMR tumors represent approximately 85% of early-stage colorectal cancers\nand have historically derived limited benefit from conventional immunotherapy\ntreatment, particularly in metastatic disease.(i,ii )In localized colon\ncancer, treatment remains centered on surgery and chemotherapy, creating a\nneed for approaches that may deepen response and reduce recurrence risk.\nAdministering immunotherapy before surgery offers a distinct biological\nopportunity to activate the immune system while the primary tumor,\ntumor-draining lymph nodes and surrounding immune microenvironment remain\nintact.\n\nThe publication adds peer-reviewed clinical and biological support for\nAgenus’ previously announced decision to prioritize BOT+BAL in\nearlier-stage, curative-intent MSS colon cancer. Agenus is advancing ROBBIN, a\nplanned global randomized Phase 3 trial evaluating neoadjuvant BOT+BAL\nfollowed by standard of care versus standard of care alone in previously\nuntreated patients with high-risk Stage II or Stage III MSS colon cancer, with\nevent-free survival as the primary endpoint. NEST’s deep tumor regression,\npre-surgical ctDNA clearance, preserved surgical timing and no observed\nrecurrences at longer follow-up supports the clinical hypothesis ROBBIN is\ndesigned to test.\n\n“NEST provides important context for Agenus’ strategic focus on\nneoadjuvant BOT+BAL in MSS colon cancer,” said Steven O’Day, M.D., Chief\nMedical Officer of Agenus. “With longer follow-up now extending beyond two\nyears across both NEST cohorts, the findings show BOT+BAL can generate deep\ntumor responses and immune activation before surgery, without delaying\nsurgery. These results strengthen the rationale for our phase 3 ROBBIN trial\nand for evaluating BOT+BAL in a curative-intent setting, where the goal is to\nreduce the risk of recurrence and improve long-term outcomes.”\n\nNEST was a single-center, open-label, single-arm Phase 2 study that enrolled\n24 eligible patients with 26 resectable colorectal tumors, including 22\npMMR/MSS tumors and four dMMR/MSI-H tumors. The study evaluated two\npre-surgical treatment intervals; approximately four weeks in NEST-1 and\napproximately eight weeks in NEST-2. Patients in both cohorts proceeded to\nplanned surgical resection without treatment-related delays.\n\nNEST Results\n\nTumor responses in pMMR/MSS disease\n\nAmong 22 pMMR/MSS tumors, neoadjuvant BOT+BAL achieved:\n\n\n * 59% pathologic response rate (pOR): defined as pathologic complete response,\nmajor pathologic response or partial response\n\n * 41% major pathologic response rate (MPR): 10% or less viable tumor remaining\n\n * 32% pathologic complete response rate (pCR): no viable tumor or adjacent lymph\nnodes found at surgery\n\nThe manuscript cites previously reported MPR rates of approximately 19% to\n20%, including pCR of approximately 10%, with first-generation CTLA-4/PD-1\ncombination therapy in pMMR colon cancer. Cross-trial comparisons should be\ninterpreted cautiously because of differences in study design, patient\npopulation and follow-up.\n\nTumor responses in dMMR/MSI-H disease\n\nAll four dMMR/MSI-H tumors achieved an MPR, including two pCR and two\nadditional tumors with near-complete tumor regression of 98% and 99%.\n\nctDNA clearance before surgery\n\nAmong patients with detectable circulating tumor DNA (ctDNA) at baseline and\navailable pre-surgical samples, 88% cleared ctDNA prior to surgery. ctDNA\nremained undetectable following resection in all patients evaluated.\n\nNo observed recurrences at longer follow-up\n\nAt the March 31, 2026 data cutoff, no colorectal cancer recurrences had been\nobserved. Median follow-up was 32.2 months in NEST-1 and 23.5 months in\nNEST-2. For external context, the FOxTROT study of neoadjuvant chemotherapy\nreported a two-year recurrence rate of 16.9%. Cross-trial comparisons should\nbe interpreted cautiously.\n\nImmune remodeling and activation in the tumor microenvironment\n\nAnalyses of paired tumor samples showed coordinated remodeling of the tumor\nimmune microenvironment in responding tumors, characterized by increased CD8+\nT-cell infiltration, reduced FOXP3+ regulatory T cells, increased CD8+/Treg\nratios and spatial reorganization of immune cells within the tumor.\n\nThese findings provide biological support for BOT’s multifunctional,\nFc-enhanced mechanism, which extends beyond conventional checkpoint blockade\nto actively remodel the immunosuppressive tumor microenvironment, and\nestablishes a mechanistic basis for activity in historically\nimmunotherapy-resistant pMMR/MSS tumors.\n\nSurgical feasibility and safety\n\nPatients proceeded to planned surgery without treatment-related delays. No\nGrade 4 treatment-related adverse events, treatment-related deaths or study\ndiscontinuations were observed.\n\n“The NEST results reinforce a major opportunity in colorectal cancer to use\nimmunotherapy earlier, before surgery, when the primary tumor and immune\nsystem are still positioned to generate a coordinated anti-tumor response,”\nsaid Pashtoon M. Kasi, M.D., M.S., Medical Director of GI Medical Oncology at\nCity of Hope Orange County, Rad Family Chair in Gastrointestinal Oncology, and\noriginator of the NEST study. “For pMMR/MSS disease, where immunotherapy has\nhistorically had limited impact, the combination of pathologic responses,\nctDNA clearance, no observed colorectal cancer recurrences at longer follow-up\nand immune remodeling is highly encouraging, particularly when viewed against\nhistorical benchmarks. These findings provide a strong foundation for\ncontinued study of neoadjuvant BOT+BAL, including NEST3, our enrolling\nmulticenter Phase 2 investigator-sponsored study.”\n\nAbout the NEST and NEST 3 Studies\n\nNEST (NCT05571293) was an investigator-initiated, single-center, open-label\nPhase 2 study evaluating neoadjuvant BOT+BAL in patients with resectable\ncolorectal cancer. The study enrolled 24 eligible patients with 26 resectable\ncolorectal tumors, including 22 with mismatch repair proficient/microsatellite\nstable and four mismatch repair deficient/microsatellite instability-high\ntumors. Patients received neoadjuvant BOT+BAL before planned surgical\nresection. The primary objectives were to assess safety, feasibility and\nanti-tumor activity, with exploratory analyses evaluating treatment-associated\nchanges in the tumor immune microenvironment. Agenus supported the study and\nprovided BOT and BAL.\n\nNEST3 (NCT07595874) is an open and actively enrolling multicenter Phase 2\ninvestigator-sponsored study evaluating neoadjuvant BOT+BAL in advanced\nresectable colorectal cancer. The study is sponsored by City of Hope Medical\nCenter, led by Pashtoon M. Kasi, M.D., M.S., as overall principal\ninvestigator, and designed to enroll approximately 100 patients across 11 U.S.\nsites. The first patient was dosed in July 2026. NEST3 is being conducted\nthrough City of Hope’s National Clinical Trials Model, a centralized\nresearch framework designed to expand patient access to clinical trials across\nmultiple City of Hope locations. More information is available at\nClinicalTrials.gov\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fclinicaltrials.gov%2Fstudy%2FNCT07595874&esheet=54594588&newsitemid=20260826183640&lan=en-US&anchor=ClinicalTrials.gov&index=3&md5=aefbc2d6b91b1018f6791a1adf604001)\n.\n\nAbout Agenus\n\nAgenus is a leading immuno-oncology company targeting cancer with a\ncomprehensive pipeline of immunological agents. The company was founded in\n1994 with a mission to expand patient populations benefiting from cancer\nimmunotherapy through combination approaches, using a broad repertoire of\nantibody therapeutics, adoptive cell therapies (through MiNK Therapeutics) and\nadjuvants. Agenus has robust end-to-end development capabilities, across\ncommercial, research and discovery. Agenus is headquartered in Lexington, MA.\nFor more information, visit www.agenusbio.com\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=http%3A%2F%2Fwww.agenusbio.com&esheet=54594588&newsitemid=20260826183640&lan=en-US&anchor=www.agenusbio.com&index=4&md5=4d798b69cc725b92a2282d3ebae1b6e5)\nor @agenus_bio. Information that may be important to investors will be\nroutinely posted on our website and social media channels.\n\nAbout Botensilimab (BOT)\n\nBotensilimab (BOT) is a human multifunctional, Fc-enhanced anti-CTLA-4\nantibody designed to boost both innate and adaptive anti-tumor immune\nresponses. Its novel design leverages mechanisms of action to extend\nimmunotherapy benefits to “cold” tumors which generally respond poorly to\nstandard of care or are refractory to conventional PD-1/CTLA-4 therapies and\ninvestigational therapies. Botensilimab augments immune responses across a\nwide range of tumor types by priming and activating T cells, reducing\nintratumoral regulatory T cells, activating myeloid cells and inducing durable\nmemory responses.\n\nApproximately 1,300 patients have been treated with botensilimab and/or\nbalstilimab in phase 1 and phase 2 clinical trials. Botensilimab alone, or in\ncombination with Agenus’ investigational PD-1 antibody, balstilimab, has\nshown clinical responses across nine metastatic, late-line cancers. For more\ninformation about botensilimab trials, visit www.clinicaltrials.gov\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=http%3A%2F%2Fwww.clinicaltrials.gov&esheet=54594588&newsitemid=20260826183640&lan=en-US&anchor=www.clinicaltrials.gov&index=5&md5=7d33a8d02c95bd9eabeab5de23598e76)\n.\n\nAbout Balstilimab (BAL)\n\nBalstilimab is a novel, fully human monoclonal immunoglobulin G4 (IgG4)\ndesigned to block PD-1 (programmed cell death protein 1) from interacting with\nits ligands PD-L1 and PD-L2. It has been evaluated in more than 900 patients\nto date and has demonstrated clinical activity and a favorable tolerability\nprofile in several tumor types.\n\nForward-Looking Statements\n\nThis press release contains forward-looking statements that are made pursuant\nto the safe harbor provisions of the federal securities laws, including\nstatements regarding its botensilimab and balstilimab programs, expected\nregulatory timelines and filings, and any other statements containing the\nwords \"may,\" \"believes,\" \"expects,\" \"anticipates,\" \"hopes,\" \"intends,\"\n\"plans,\" \"forecasts,\" \"estimates,\" \"will,\" “establish,” “potential,”\n“superiority,” “best in class,” and similar expressions are intended\nto identify forward-looking statements. These forward-looking statements are\nsubject to risks and uncertainties that could cause actual results to differ\nmaterially. These risks and uncertainties include, among others, the factors\ndescribed under the Risk Factors section of our most recent Annual Report on\nForm 10-K for 2025, and subsequent Quarterly Reports on Form 10-Q filed with\nthe Securities and Exchange Commission. Agenus cautions investors not to place\nconsiderable reliance on the forward-looking statements contained in this\nrelease. These statements speak only as of the date of this press release, and\nAgenus undertakes no obligation to update or revise the statements, other than\nto the extent required by law. All forward-looking statements are expressly\nqualified in their entirety by this cautionary statement.\n _________________________                                \n References                                               \n                                                          \n (i )Buchler T. Front Oncol. 2022;12:888181.              \n (ii) Guven DC, et al. Oncologist. 2024;29(5):e580-e600.  \n\n\n \n\n\n\nView source version on businesswire.com:\nhttps://www.businesswire.com/news/home/20260826183640/en/\n(https://www.businesswire.com/news/home/20260826183640/en/)\n\nInvestors \n\n917-362-1370 | investor@agenusbio.com (mailto:investor@agenusbio.com)\n\nMedia \n\n781-674-4422 | communications@agenusbio.com\n(mailto:communications@agenusbio.com)\n\n\nCopyright Business Wire 2026","article_body_html":"","raw_payload":{"data":{"id":"nBwcb1GgYa","title":"Agenus Announces Updated NEST Phase 2 Publication Reporting Deep Pathologic Responses and No Observed Recurrences with Neoadjuvant BOT+BAL in Resectable Colon Cancer","author":"Business Wire","ticker":"AGEN","created":"2026-08-26T14:05:00.098Z","tickers":["AGEN"],"exchange":"NASDAQ","article_body":"Agenus Announces Updated NEST Phase 2 Publication Reporting Deep Pathologic\nResponses and No Observed Recurrences with Neoadjuvant BOT+BAL in Resectable\nColon Cancer\n\n\n * No colorectal cancer recurrences observed at updated median follow-up of 32.2\nmonths in NEST-1 and 23.5 months in NEST-2\n\n * In pMMR/MSS tumors, neoadjuvant BOT+BAL achieved 59% pathologic response,\nincluding 41% major pathologic response and 32% pathologic complete response\n\n * 88% of evaluable patients cleared ctDNA before surgery, with no delays to\nplanned surgical resection\n\n * Longer follow-up and immune analysis provide clinical and biological support\nfor Agenus’ planned global Phase 3 ROBBIN trial in curative-intent MSS/pMMR\ncolon cancer\n\nAgenus\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=http%3A%2F%2Fwww.agenusbio.com&esheet=54594588&newsitemid=20260826183640&lan=en-US&anchor=Agenus&index=1&md5=7dc2a3fc88e094e49d5320b5df32e498)\nInc. (Nasdaq: AGEN), a leader in immuno-oncology innovation, today announced\nthe peer-reviewed publication of updated results from the\ninvestigator-sponsored Phase 2 NEST trial evaluating neoadjuvant botensilimab\n(BOT), Agenus’ multifunctional, Fc-enhanced anti-CTLA-4 antibody, and\nbalstilimab (BAL), Agenus’ anti-PD-1 antibody, in patients with resectable\ncolon cancer. The manuscript, titled “Neoadjuvant botensilimab/balstilimab\nfor localized mismatch repair proficient and deficient colon cancer: Results\nof the NEST phase 2 clinical trial,” was published in Clinical Cancer\nResearch and is available here\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Faacrjournals.org%2Fclincancerres%2Farticle%2Fdoi%2F10.1158%2F1078-0432.CCR-26-0998%2F787654%2FNeoadjuvant-Botensilimab-Balstilimab-for-localized&esheet=54594588&newsitemid=20260826183640&lan=en-US&anchor=here&index=2&md5=65ad473756164432fd3df2f6a439dbb3)\n.\n\nEarlier findings from NEST were presented at the 2025 ASCO Gastrointestinal\nCancers Symposium. The publication provides longer follow-up and a fuller\npeer-reviewed analysis of tumor responses, circulating tumor DNA (ctDNA)\ndynamics, disease-free follow-up and immune changes in the tumor\nmicroenvironment.\n\nAt the March 31, 2026 data cutoff, no colorectal cancer recurrences had been\nobserved, with median follow-up of 32.2 months in NEST-1 and 23.5 months in\nNEST-2. Among 22 mismatch repair proficient/microsatellite stable (pMMR/MSS)\ntumors, 59% achieved a pathologic response, including 41% with a major\npathologic response and 32% with a pathologic complete response.\n\nMSS/pMMR tumors represent approximately 85% of early-stage colorectal cancers\nand have historically derived limited benefit from conventional immunotherapy\ntreatment, particularly in metastatic disease.(i,ii )In localized colon\ncancer, treatment remains centered on surgery and chemotherapy, creating a\nneed for approaches that may deepen response and reduce recurrence risk.\nAdministering immunotherapy before surgery offers a distinct biological\nopportunity to activate the immune system while the primary tumor,\ntumor-draining lymph nodes and surrounding immune microenvironment remain\nintact.\n\nThe publication adds peer-reviewed clinical and biological support for\nAgenus’ previously announced decision to prioritize BOT+BAL in\nearlier-stage, curative-intent MSS colon cancer. Agenus is advancing ROBBIN, a\nplanned global randomized Phase 3 trial evaluating neoadjuvant BOT+BAL\nfollowed by standard of care versus standard of care alone in previously\nuntreated patients with high-risk Stage II or Stage III MSS colon cancer, with\nevent-free survival as the primary endpoint. NEST’s deep tumor regression,\npre-surgical ctDNA clearance, preserved surgical timing and no observed\nrecurrences at longer follow-up supports the clinical hypothesis ROBBIN is\ndesigned to test.\n\n“NEST provides important context for Agenus’ strategic focus on\nneoadjuvant BOT+BAL in MSS colon cancer,” said Steven O’Day, M.D., Chief\nMedical Officer of Agenus. “With longer follow-up now extending beyond two\nyears across both NEST cohorts, the findings show BOT+BAL can generate deep\ntumor responses and immune activation before surgery, without delaying\nsurgery. These results strengthen the rationale for our phase 3 ROBBIN trial\nand for evaluating BOT+BAL in a curative-intent setting, where the goal is to\nreduce the risk of recurrence and improve long-term outcomes.”\n\nNEST was a single-center, open-label, single-arm Phase 2 study that enrolled\n24 eligible patients with 26 resectable colorectal tumors, including 22\npMMR/MSS tumors and four dMMR/MSI-H tumors. The study evaluated two\npre-surgical treatment intervals; approximately four weeks in NEST-1 and\napproximately eight weeks in NEST-2. Patients in both cohorts proceeded to\nplanned surgical resection without treatment-related delays.\n\nNEST Results\n\nTumor responses in pMMR/MSS disease\n\nAmong 22 pMMR/MSS tumors, neoadjuvant BOT+BAL achieved:\n\n\n * 59% pathologic response rate (pOR): defined as pathologic complete response,\nmajor pathologic response or partial response\n\n * 41% major pathologic response rate (MPR): 10% or less viable tumor remaining\n\n * 32% pathologic complete response rate (pCR): no viable tumor or adjacent lymph\nnodes found at surgery\n\nThe manuscript cites previously reported MPR rates of approximately 19% to\n20%, including pCR of approximately 10%, with first-generation CTLA-4/PD-1\ncombination therapy in pMMR colon cancer. Cross-trial comparisons should be\ninterpreted cautiously because of differences in study design, patient\npopulation and follow-up.\n\nTumor responses in dMMR/MSI-H disease\n\nAll four dMMR/MSI-H tumors achieved an MPR, including two pCR and two\nadditional tumors with near-complete tumor regression of 98% and 99%.\n\nctDNA clearance before surgery\n\nAmong patients with detectable circulating tumor DNA (ctDNA) at baseline and\navailable pre-surgical samples, 88% cleared ctDNA prior to surgery. ctDNA\nremained undetectable following resection in all patients evaluated.\n\nNo observed recurrences at longer follow-up\n\nAt the March 31, 2026 data cutoff, no colorectal cancer recurrences had been\nobserved. Median follow-up was 32.2 months in NEST-1 and 23.5 months in\nNEST-2. For external context, the FOxTROT study of neoadjuvant chemotherapy\nreported a two-year recurrence rate of 16.9%. Cross-trial comparisons should\nbe interpreted cautiously.\n\nImmune remodeling and activation in the tumor microenvironment\n\nAnalyses of paired tumor samples showed coordinated remodeling of the tumor\nimmune microenvironment in responding tumors, characterized by increased CD8+\nT-cell infiltration, reduced FOXP3+ regulatory T cells, increased CD8+/Treg\nratios and spatial reorganization of immune cells within the tumor.\n\nThese findings provide biological support for BOT’s multifunctional,\nFc-enhanced mechanism, which extends beyond conventional checkpoint blockade\nto actively remodel the immunosuppressive tumor microenvironment, and\nestablishes a mechanistic basis for activity in historically\nimmunotherapy-resistant pMMR/MSS tumors.\n\nSurgical feasibility and safety\n\nPatients proceeded to planned surgery without treatment-related delays. No\nGrade 4 treatment-related adverse events, treatment-related deaths or study\ndiscontinuations were observed.\n\n“The NEST results reinforce a major opportunity in colorectal cancer to use\nimmunotherapy earlier, before surgery, when the primary tumor and immune\nsystem are still positioned to generate a coordinated anti-tumor response,”\nsaid Pashtoon M. Kasi, M.D., M.S., Medical Director of GI Medical Oncology at\nCity of Hope Orange County, Rad Family Chair in Gastrointestinal Oncology, and\noriginator of the NEST study. “For pMMR/MSS disease, where immunotherapy has\nhistorically had limited impact, the combination of pathologic responses,\nctDNA clearance, no observed colorectal cancer recurrences at longer follow-up\nand immune remodeling is highly encouraging, particularly when viewed against\nhistorical benchmarks. These findings provide a strong foundation for\ncontinued study of neoadjuvant BOT+BAL, including NEST3, our enrolling\nmulticenter Phase 2 investigator-sponsored study.”\n\nAbout the NEST and NEST 3 Studies\n\nNEST (NCT05571293) was an investigator-initiated, single-center, open-label\nPhase 2 study evaluating neoadjuvant BOT+BAL in patients with resectable\ncolorectal cancer. The study enrolled 24 eligible patients with 26 resectable\ncolorectal tumors, including 22 with mismatch repair proficient/microsatellite\nstable and four mismatch repair deficient/microsatellite instability-high\ntumors. Patients received neoadjuvant BOT+BAL before planned surgical\nresection. The primary objectives were to assess safety, feasibility and\nanti-tumor activity, with exploratory analyses evaluating treatment-associated\nchanges in the tumor immune microenvironment. Agenus supported the study and\nprovided BOT and BAL.\n\nNEST3 (NCT07595874) is an open and actively enrolling multicenter Phase 2\ninvestigator-sponsored study evaluating neoadjuvant BOT+BAL in advanced\nresectable colorectal cancer. The study is sponsored by City of Hope Medical\nCenter, led by Pashtoon M. Kasi, M.D., M.S., as overall principal\ninvestigator, and designed to enroll approximately 100 patients across 11 U.S.\nsites. The first patient was dosed in July 2026. NEST3 is being conducted\nthrough City of Hope’s National Clinical Trials Model, a centralized\nresearch framework designed to expand patient access to clinical trials across\nmultiple City of Hope locations. More information is available at\nClinicalTrials.gov\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fclinicaltrials.gov%2Fstudy%2FNCT07595874&esheet=54594588&newsitemid=20260826183640&lan=en-US&anchor=ClinicalTrials.gov&index=3&md5=aefbc2d6b91b1018f6791a1adf604001)\n.\n\nAbout Agenus\n\nAgenus is a leading immuno-oncology company targeting cancer with a\ncomprehensive pipeline of immunological agents. The company was founded in\n1994 with a mission to expand patient populations benefiting from cancer\nimmunotherapy through combination approaches, using a broad repertoire of\nantibody therapeutics, adoptive cell therapies (through MiNK Therapeutics) and\nadjuvants. Agenus has robust end-to-end development capabilities, across\ncommercial, research and discovery. Agenus is headquartered in Lexington, MA.\nFor more information, visit www.agenusbio.com\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=http%3A%2F%2Fwww.agenusbio.com&esheet=54594588&newsitemid=20260826183640&lan=en-US&anchor=www.agenusbio.com&index=4&md5=4d798b69cc725b92a2282d3ebae1b6e5)\nor @agenus_bio. Information that may be important to investors will be\nroutinely posted on our website and social media channels.\n\nAbout Botensilimab (BOT)\n\nBotensilimab (BOT) is a human multifunctional, Fc-enhanced anti-CTLA-4\nantibody designed to boost both innate and adaptive anti-tumor immune\nresponses. Its novel design leverages mechanisms of action to extend\nimmunotherapy benefits to “cold” tumors which generally respond poorly to\nstandard of care or are refractory to conventional PD-1/CTLA-4 therapies and\ninvestigational therapies. Botensilimab augments immune responses across a\nwide range of tumor types by priming and activating T cells, reducing\nintratumoral regulatory T cells, activating myeloid cells and inducing durable\nmemory responses.\n\nApproximately 1,300 patients have been treated with botensilimab and/or\nbalstilimab in phase 1 and phase 2 clinical trials. Botensilimab alone, or in\ncombination with Agenus’ investigational PD-1 antibody, balstilimab, has\nshown clinical responses across nine metastatic, late-line cancers. For more\ninformation about botensilimab trials, visit www.clinicaltrials.gov\n(https://cts.businesswire.com/ct/CT?id=smartlink&url=http%3A%2F%2Fwww.clinicaltrials.gov&esheet=54594588&newsitemid=20260826183640&lan=en-US&anchor=www.clinicaltrials.gov&index=5&md5=7d33a8d02c95bd9eabeab5de23598e76)\n.\n\nAbout Balstilimab (BAL)\n\nBalstilimab is a novel, fully human monoclonal immunoglobulin G4 (IgG4)\ndesigned to block PD-1 (programmed cell death protein 1) from interacting with\nits ligands PD-L1 and PD-L2. It has been evaluated in more than 900 patients\nto date and has demonstrated clinical activity and a favorable tolerability\nprofile in several tumor types.\n\nForward-Looking Statements\n\nThis press release contains forward-looking statements that are made pursuant\nto the safe harbor provisions of the federal securities laws, including\nstatements regarding its botensilimab and balstilimab programs, expected\nregulatory timelines and filings, and any other statements containing the\nwords \"may,\" \"believes,\" \"expects,\" \"anticipates,\" \"hopes,\" \"intends,\"\n\"plans,\" \"forecasts,\" \"estimates,\" \"will,\" “establish,” “potential,”\n“superiority,” “best in class,” and similar expressions are intended\nto identify forward-looking statements. These forward-looking statements are\nsubject to risks and uncertainties that could cause actual results to differ\nmaterially. These risks and uncertainties include, among others, the factors\ndescribed under the Risk Factors section of our most recent Annual Report on\nForm 10-K for 2025, and subsequent Quarterly Reports on Form 10-Q filed with\nthe Securities and Exchange Commission. Agenus cautions investors not to place\nconsiderable reliance on the forward-looking statements contained in this\nrelease. These statements speak only as of the date of this press release, and\nAgenus undertakes no obligation to update or revise the statements, other than\nto the extent required by law. All forward-looking statements are expressly\nqualified in their entirety by this cautionary statement.\n _________________________                                \n References                                               \n                                                          \n (i )Buchler T. Front Oncol. 2022;12:888181.              \n (ii) Guven DC, et al. Oncologist. 2024;29(5):e580-e600.  \n\n\n \n\n\n\nView source version on businesswire.com:\nhttps://www.businesswire.com/news/home/20260826183640/en/\n(https://www.businesswire.com/news/home/20260826183640/en/)\n\nInvestors \n\n917-362-1370 | investor@agenusbio.com (mailto:investor@agenusbio.com)\n\nMedia \n\n781-674-4422 | communications@agenusbio.com\n(mailto:communications@agenusbio.com)\n\n\nCopyright Business Wire 2026"},"type":"article","timestamp":"2026-08-26T14:05:00.329944704Z","server_sent_at_ms":1787753100329},"received_at":"2026-08-26T14:05:00.481Z","source_url":"https://www.businesswire.com/news/home/20260826183640/en/"},"analysis":{"id":"117296","press_release_id":"128381","analysis_json":{"industry":{"label":"Biotechnology","sector":"Health Care"},"redFlags":[],"eventType":"clinical_trial","narrative":"Agenus announced updated results from the Phase 2 NEST trial showing neoadjuvant BOT+BAL achieved 32% pathologic complete response with no observed recurrences in MSS/pMMR colon cancer.\n\nThe data revealed 88% of evaluable patients cleared ctDNA before surgery, and median follow-up extended to 32.2 months without treatment delays or Grade 4 adverse events.\n\nThese findings support the strategic pivot to the planned global Phase 3 ROBBIN trial in curative-intent settings.","sentiment":"bullish","agentHooks":{"shouldPost":true,"suggestedAngle":"Zero recurrences and high pCR rates in MSS colon cancer position Agenus for a pivotal Phase 3 readout."},"keyFigures":{"drugName":"botensilimab (BOT) + balstilimab (BAL)","phaseOfTrial":"Phase 2","customDimensions":{"MPR_rate":"41%","pCR_rate":"32%","pOR_rate":"59%","ctDNA_clearance_rate":"88%","median_follow_up_nest1":"32.2 months","median_follow_up_nest2":"23.5 months"}},"quotedText":"With longer follow-up now extending beyond two years across both NEST cohorts, the findings show BOT+BAL can generate deep tumor responses and immune activation before surgery, without delaying surgery.","namedEntities":{"people":[{"name":"Steven O’Day","role":"Chief Medical Officer"},{"name":"Pashtoon M. 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