Botensilimab

Deep and durable responses observed in a heavily pretreated, historically immunotherapy-resistant population Findings reinforce the broad, pan-tumor activity of BOT+BAL across immunologically “cold” cancers LEXINGTON, Mass.--(BUSINESS WIRE)-- $AGEN #BAL -- Agenus Inc. (Nasdaq: AGEN) , a leader in immuno-oncology innovation, today announced the publication of clinical results from the ovarian cancer cohort of its Phase 1b C-800-01 trial evaluating botensilimab plus balstilimab (BOT+BAL) in The Journal for ImmunoTherapy of Cancer (JITC) . The peer-reviewed manuscript titled, “Botensilimab (Fc-enhanced anti–CTLA-4 antibody) plus balstilimab (anti–PD-1 antibody) in patients with treatment-refractory ovarian cancer,” is available online here . i In this heavily pretreated population, BOT+BAL demonstrated clinically meaningful activity and durable benefit in women with treatment-refractory ovarian cancer, a population with few remaining options. The combination achieved a 23% overall response rate and 31% clinical benefit rate, including durable responses with a median duration of 9.7 months. Median overall survival reached 14.8 months, with an estimated of 75% of patients alive at 12 months. These findings build on results from the broader C-800-01 dataset presented at ESMO 2025, where BOT+BAL showed activity across multiple refractory solid tumors. Collectively, these data reinforce the potential of BOT+BAL to generate meaningful immune responses in cancers historically considered unresponsive to immunotherapy. High Unmet Need in Treatment-Refractory Ovarian Cancer Ovarian cancer causes approximately 13,000 deaths annually in the U.S. and 200,000 globally ii,iii , and outcomes are particularly poor once tumors become platinum-resistant or platinum-refractory. Therapy with first-generation checkpoint inhibitors has yielded modest responses, with objective response rates between 8–10% and median progression-free survival of roughly 2 months iv,v , leaving many women with rapidly diminishing options and no approved immunotherapy combinations. Publication Highlights The study enrolled 44 women with treatment-refractory ovarian cancer who had received multiple prior lines of therapy. Nearly three-quarters were platinum-resistant or platinum-refractory, and most had high-grade serous tumors. Activity was demonstrated in primary platinum-refractory patients—a rare and high-risk group often excluded from clinical studies. Responses occurred in multiple ovarian cancer subtypes including high-grade serous, clear cell, and endometrioid tumors. The BOT+BAL combination demonstrated a manageable and reversible safety profile, consistent with CTLA-4 and PD-1 therapy. Most common treatment-related adverse events such as diarrhea/colitis (43%; 16% grade 3), fatigue and nausea (36%) were effectively managed using established treatment guidelines. No treatment-related deaths were reported. Steven O’Day, MD, Chief Medical Officer, Agenus, commented, “These results offer a meaningful signal of clinical activity for women with platinum-refractory ovarian cancer, a group that has seen little therapeutic progress. Botensilimab’s unique immune activation pro into clinically significant responses in a population long considered resistant to immunotherapy. These findings strengthen our confidence in BOT+BAL’s potential and support moving this combination into larger, randomized studies.” Rebecca Porter, M.D., Ph.D., Dana-Farber Cancer Institute and Lead Author added, “These women faced some of the most treatment-resistant forms of ovarian cancer, yet several achieved meaningful and durable benefit. Seeing this level of activity in such a heavily pretreated population is encouraging and provides important insights to the field regarding therapy approaches for patients with very limited remaining options.” Patient Access and Ongoing Development BOT+BAL continues to advance through global clinical development across multiple tumor types. In parallel, eligible patients may be able to access BOT+BAL through regulatory-authorized early access mechanisms, including France’s AAC program, where treatment is reimbursed, as well as paid named-patient programs in select countries where permitted by local regulations. These programs are intended to provide access for patients with serious or life-threatening diseases who lack satisfactory therapeutic alternatives. 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. 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 or @agenus_bio. Information that may be important to investors will be routinely posted on our website and social media channels. About the C-800-01 Study C-800-01 (NCT03860272) is an ongoing, multicenter Phase 1b clinical trial evaluating botensilimab in combination with balstilimab across advanced solid tumors. The trial enrolled over 400 patients with refractory disease and included tumor types with limited or no responsiveness to prior checkpoint inhibitors. Endpoints included objective response rate (ORR), duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Results of the study were presented at ESMO 2025 and the full presentation is available on the publications page of the Agenus website here . About Botensilimab (BOT) Botensilimab (BOT) is a human Fc enhanced multifunctional anti-CTLA-4 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. Approximately 1,200 patients have been treated with botensilimab and/or balstilimab in phase 1 and phase 2 clinical trials. Botensilimab alone, or in combination with Agenus’ investigational PD-1 antibody, balstilimab, has shown clinical responses across nine metastatic, late-line cancers. For more information about botensilimab trials, visit . 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 more than 900 patients to date and has demonstrated clinical activity and a favorable tolerability pro 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. ____________________________ i Porter R, Bockorny B, Corr BR, et al. Botensilimab (Fc-enhanced anti–CTLA-4 antibody) plus balstilimab (anti–PD-1 antibody) in patients with treatment-refractory ovarian cancer. J Immunother Cancer. 2025;13(12)e:013222. doi:10.1136/jitc-2025-013222. ii Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA Cancer J Clin 2024;74:12–49. iii Sung H, Ferlay J, Siegel RL, et al . Global Cancer Statistics 2020:GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin 2021;71:209–49. iv Disis ML, Taylor MH, Kelly K, et al . Efficacy and Safety of Avelumab for Patients With Recurrent or Refractory Ovarian Cancer: Phase 1b Results From the JAVELIN Solid Tumor Trial. JAMA Oncol 2019;5:393–401. v Matulonis UA, Shapira-Frommer R, Santin AD, et al . Antitumor activity and safety of pembrolizumab in patients with advanced recurrent ovarian cancer: results from the phase II KEYNOTE-100 study. Ann Oncol 2019;30:1080–7. Contacts Investors 917-362-1370 | investor@agenusbio.com Media 781-674-4422 | communications@agenusbio.com

Endpoints News sat down with Jeff Bluestone and Stephen Dilly after Sonoma Biotherapeutics announced earlier this week that Bluestone was stepping down from his CEO role and Dilly would be taking his place. Bluestone, a prominent academic and the first head of the Parker Institute for Cancer Immunotherapy, founded Sonoma six years ago to develop regulatory T cell therapies. On Monday, he handed the reins to Sonoma over to Dilly, the former CEO of Codexis and Sierra Oncology . This conversation has been substantially edited for length and clarity. Lei Lei Wu: Jeff, I’ll start with you. Not too long ago, we met to speak about Sonoma’s first clinical data. How long has this transition been in the works for? And why now? Jeff Bluestone: We needed to go find a great CEO. It took me a little bit more than 24 hours to do that, so we started the search a little while ago. But, very excited to have Stephen come on board. I just felt it was the right time to turn the reins over, because I think the company is a really great place right now. Someone emailed me this morning and said it’s a little bit like [Los Angeles Dodgers Hall of Famer] Sandy Koufax . In his last year, he was an All-Star pitcher, shutouts every day. And I figured, might as well leave on a good note. Plus my grandkids, my wife and the rest of my life had a big impact as well. Wu: Are you a Dodgers fan? Bluestone: No, not at all. My father grew up a New York Giants fan, and we hated the Yankees and we hated the Dodgers. Wu: What’s next for you? Bluestone: It’s hard to use the word “retire.” It feels like a definitive ending, which it won’t be. I’m really lucky that Stephen is interested in having me continue to advise the company, which I will, and I’ll be on the board. Aside from that, I’m on the Gilead board, which I’ll continue to do, and then I want to spend some time thinking about how I can help young people. The idea of being able to help young student scientists is exciting to me. I’ll probably go back to UCSF for journal clubs and lab meetings and the like. And then finally, just do some of the things in life that I sacrificed over these many years. Wu: Stephen, turning to you now. What made you interested in this role? Stephen Dilly: One of the things that I believe in very strongly is that people are ideally suited to stages of journeys. What Jeff has done over the last six years at Sonoma, something that I would not be able to do, is take basic science and incredible insights and turn that from a concept into something that’s ready for going into people. I’m a drug developer. Dyed-in-the-wool drug developer. It’s a different thought process. The research process is inclusive and exploratory. The development process is very targeted. A lot of it is about the way you look at challenges, the way you address them, the way you move forward. And this company is absolutely in my sweet spot. A lot of the raw material is here to do something quite remarkable. — Lei Lei Wu → T cell receptor specialist Adaptimmune announced on Monday that its CEO of six years, Adrian Rawcliffe , left “in connection with the company’s restructuring.” It’s the end of an era for Adaptimmune, which won approval last year for the first cell therapy based on T cell receptors. Known as Tecelra , the therapy was approved for a rare cancer called synovial sarcoma. The news comes after Adaptimmune sold Tecelra , among other assets, and laid off nearly two-thirds of its workforce. Most of the company’s executives departed with the layoffs, and Rawcliffe is the latest to do so. Chris Hill is now CEO as well as CFO. And the company’s longtime COO William Bertrand also left “in connection with the restructuring,” Adaptimmune said Monday . → Former FDA Commissioner Scott Gottlieb has joined UnitedHealth Group ’s board, the massive health insurer said Tuesday. Gottlieb also sits on the boards of Pfizer and Illumina . The move comes as UnitedHealth has faced increasing pressure on its business with higher medical costs and scrutiny over insurance denials , as well as a ransomware attack on its Change Healthcare business. Former CEO Andrew Witty stepped down in May and was replaced by longtime UnitedHealth chief Stephen Hemsley . Its stock is down 38% this year. “We welcome his deep expertise and thought leadership as we strive to help people live healthier lives and make the health system work better for everyone,” Hemsley said in a news release . → Juby Chandy will have new responsibilities at GSK on Dec. 1: The current GSK India CFO has been named VP of finance for the Asia Pacific region. Scrolling is required to go through Chandy’s 17-year career at GSK, where he has also served as area finance director for Southeast Asia and head of finance, general medicines, global pharma, among other roles. In October, Emma Walmsley conducted her last quarterly report at GSK before commercial chief Luke Miels takes over as CEO. → Philina Lee will be the next CEO at Sydney-based cancer biotech AdvanCell on Jan. 1. She’ll replace Andrew Adamovich , who will have a new role as managing director, Australia. Lee will take over a company that just stocked up on cash with a $112 million Series C in February. She had an 11-year run at Blueprint Medicines and was chief commercial officer until Sanofi bought the Ayvakit maker for more than $9 billion this year. (Incidentally, her former boss Kate Haviland said on LinkedIn this week that she’ll “continue contributing to the life sciences ecosystem” as a senior advisor at Jefferies .) AdvanCell’s lead program 212Pb-ADVC001 is a PSMA-targeting radioligand for patients with prostate cancer. “Philina’s leadership further strengthens our ability to establish the United States as a global hub while continuing to deliver innovation from Australia and cementing our position as a leader in targeted alpha radiotherapies,” Adamovich said in a statement . → At another Australian drugmaker, Mesoblast has tapped Bristol Myers Squibb and Allergan vet James O’Brien as CFO. O’Brien will be based in the US and was CFO at Cognition Therapeutics (2019-23) and Faron Pharmaceuticals (2023-24). Mesoblast’s head of finance Andrew Chaponnel had been interim finance chief since Josh Muntner hit the exit in 2021. At long last, the FDA approved Mesoblast’s mesenchymal stromal cell therapy Ryoncil in December 2024. → Gilead general counsel Deborah Telman will leave on Dec. 5, according to a terse SEC filing . Telman replaced Brett Pletcher as EVP, corporate affairs and general counsel in August 2022. Gilead did not provide any details about Telman’s departure. → As part of a restructuring, Nxera Pharma is trimming its leadership team, going from 10 execs to seven by March 2026 in a bid to cut operating expenses. Nxera is also pruning its workforce by about 15% across Japan and the UK, and focusing its sights on obesity, metabolic and endocrine therapies. While the company is cutting jobs elsewhere, it has recruited Patrik Foerch as CSO and president of Nxera Pharma UK , taking over the reins from Matthew Barnes . Foerch was CSO of Peptone , ran preclinical drug discovery at Sitryx , and had a 13-year stint at UCB . Nxera hopes that the cost-cutting measures will help the company reach its net sales forecast of 50 billion yen in 2030. → With ex- NGM Bio CEO David Woodhouse now at the controls, immunomodulatory upstart Nuvig Therapeutics has welcomed Celia Lin as CMO. Lin joined Santa Ana Bio in the same capacity shortly after the Versant biotech’s $125 million Series B last summer, but she stepped down nine months later. Peer Review covered Lin’s appointment as CMO of Vera Therapeutics and her departure in early 2024, when she was replaced by Robert Brenner . Nuvig disclosed a nine-figure Series B of its own last year and is evaluating NVG-2089 in chronic inflammatory demyelinating polyneuropathy (CIDP) and immune thrombocytopenia. → Paolo Tombesi is retiring after CFO posts at multiple drugmakers over the past 25 years. He’s handing the job at Athena Countouriotis ’ Avenzo Therapeutics to Scott Lipman , who was promoted to CBO last year and will retain both duties. Tombesi helped Countouriotis steer their prior biotech, Turning Point Therapeutics , toward a multibillion-dollar exit to Bristol Myers Squibb . Along with Lipman, they reunited for Avenzo, raising more than $440 million over the past few years for small molecules and antibody-drug conjugates licensed from Chinese partners. Prior to that, Tombesi built his CFO chops at Epizyme and Insmed after holding regional CFO posts at Novartis and Bristol Myers. → 4D Molecular Therapeutics has found a new CFO after Uneek Mehra ’s departure in July. Kristian Humer held this job title at Foghorn Therapeutics and Viridian Therapeutics after 11 years with the healthcare investment banking group at Citi . Mehra took the CFO job at BridgeBio Oncology Therapeutics , or BBOT. Shares $FDMT surged this summer when 4DMT notched a Phase 2 win with its gene therapy 4D-150 for diabetic macular edema, and there’s been an upward trend ever since. → Andy Nichols announced on LinkedIn that he’s “finally pulling the plug and disconnecting from corporate life, at least for a while,” after 40 years in the industry and two years at Jazz Pharmaceuticals as SVP of research, nonclinical development and clinical pharmacology. By the way, Zymeworks has named EcoR1 Capital partner Scott Platshon as acting chief investment officer. Jazz and Zymeworks outlined a Phase 3 win this week with their HER2 bispecific Ziihera in gastroesophageal adenocarcinoma, and their stock prices popped as a result. → Abraxane developer José Iglesias ’ first day as chief medical affairs officer at Agenus was Nov. 10, according to a Tuesday press release . Iglesias had a brief turn as CMO at Tim Lu ’s Senti Bio in 2020, and he reemerged as consulting medical chief for Panavance Therapeutics . Agenus is combining its anti-CTLA-4 antibody botensilimab with its PD-1 candidate balstilimab . Known colloquially as BOT/BAL , the combo is in Phase 3 for microsatellite-stable colorectal cancer. → French ADC maker Adcytherix has hired a pair of execs after a host of investors participated in its €105 million Series A . Medical chief Jan Schellens just held the same position at another ADC developer in France called Skymab Biotherapeutics , and he was CMO of Dutch biotech Byondis from 2019-23. Finance chief Jaime Arango had multiple roles over a nine-period at Merck , and he’s been CFO at Medincell and TreeFrog Therapeutics . → Eduardo Dunayevich will help steer the clinical direction of San Francisco-based Neurona Therapeutics , the CNS cell therapy startup that nabbed $ 102 million earlier this year for its epilepsy program. The new CMO was VP of clinical development and leader of the VMAT2 franchise at Neurocrine Biosciences . Dunayevich has been in industry for a quarter-century, making stops at Eli Lilly , Orexigen Therapeutics , Amgen , Takeda , Annexon Biosciences and Greenwich Biosciences along the way. → Elicio Therapeutics , co-founded by former MIT professor Darrell Irvine , has selected Marc Wolfgang as chief technology officer. Wolfgang just finished a stint as SVP of technical development and operations over at Flagship ’s Sail Biomedicines , which cut 30% of its staff in July. Wolfgang’s résumé also includes gigs at BioNTech , Cerulean Pharma , Momenta Pharmaceuticals , Millennium Pharmaceuticals , Biogen and Boehringer Ingelheim . → Kameel Farag helped set up cell therapy maker Aspen Neuroscience for a potential IPO (with a $115 million Series C disclosed Thursday). Now, a few months after leaving the CFO post at Aspen, he’s returning to the role on an interim basis at Akari Therapeutics . Farag built up his finance acumen during a 16-year career at Amgen and a three-year stint at Ionis . Akari has two ADC programs in preclinical development. → After bagging Y-mAbs in a $412 million all-cash deal , specialty drugmaker SERB Pharmaceuticals is bringing its CMO into the fold. Vignesh Rajah will serve in the same role of medical chief at SERB. Besides Y-mAbs, Rajah had roles at Sanofi and Wyeth , as well as a decade-long career at GSK. SERB picked up Y-mAbs and its neuroblastoma treatment Danyelza in August, hoping to further expand upon its own portfolio of more than 70 drugs. → Mosaic Therapeutics CEO Thomas Fuchs is already making an impact in his first month on the job, bringing in Samsara BioCapital venture partner Stephen Shuttleworth as CSO. AstraZeneca vet Barry Davies is retiring from the position and will be “on extended gardening and travel leave,” according to his LinkedIn. Shuttleworth was CSO, COO and executive director at Karus Therapeutics , and he chaired the scientific advisory board at the end of his 12-year career with the company. → To the Dallas metro area we go, where OncoNano Medicine has lassoed Brent Sorrells as COO. Sorrells spent eight years with Allakos , where he was promoted to VP of product development and strategy in mid-2024. Concentra Biosciences scooped up the biotech earlier this year, setting off a chain reaction of similar acquisitions for Kevin Tang . OncoNano is developing a STING agonist called ONM-501 for solid tumors. → Edgewise Therapeutics has welcomed Chris Martin to the board of directors, following the appointment of CFO Michael Nofi . Martin helped launch the COPD treatment Ohtuvayre as chief commercial officer at Verona Pharma . Merck bought Verona this summer for $10 billion. Lydia Ramsey Pflanzer contributed to this edition.