Agenus (NASDAQ:AGEN) said it is shifting its development focus and financial resources toward a Phase 3 registrational trial of neoadjuvant botensilimab plus balstilimab, known as BOT/BAL, in high-risk stage 2 and stage 3 microsatellite stable colon cancer.
Founder, Chairman and Chief Executive Officer Garo Armen said the company views the neoadjuvant setting in MSS colon cancer as its “highest impact and highest value opportunity.” MSS colon cancer accounts for about 85% of colon cancers and has historically been refractory to conventional immunotherapy, according to Agenus executives on the webcast.
Garo Armen said the $85 million upfront payment is expected to remove near-term financing pressure. If warrants are fully exercised, he said the structure is intended to fund the ROBBIN trial and Agenus operations through year-end 2031.
Agenus Frames ROBBIN as Core Development Priority
The ROBBIN trial is designed to evaluate neoadjuvant BOT/BAL in high-risk stage 2 and stage 3 MSS colon cancer. Dr. Steven O’Day, Agenus’ chief medical officer, said the global, randomized Phase 3 study is expected to enroll approximately 850 patients.
The study will compare six to eight weeks of neoadjuvant botensilimab plus balstilimab followed by surgery against immediate surgery within the first four weeks. Both arms will receive standard adjuvant chemotherapy based on surgical pathologic staging. The primary endpoint is event-free survival.
O’Day said the trial is powered around a target event-free survival hazard ratio of 0.65, with an interim event-free survival analysis planned at 75% of events and a final analysis after 100% of events. He said the FDA has aligned around key elements of the Phase 3 design, including the patient population, treatment arms and primary registrational endpoint.
Agenus is targeting first patient enrollment in the first quarter of 2027, an interim top-line pathologic response readout by the end of 2027, an interim event-free survival analysis in the second half of 2029 and final analysis in the second half of 2030.
Company Highlights Unmet Need in MSS Colon Cancer
Robin Taylor, Agenus’ chief commercial officer, said colorectal cancer is the leading cause of cancer-related death among Americans under 50. Across all ages, she cited U.S. annual disease incidence of 155,000 cases, with about 70% being colon cancer.
Taylor said roughly 38,000 high-risk stage 2 and stage 3 MSS colon cancer patients are treated annually in the U.S. She characterized the commercial opportunity as distinct from late-line metastatic disease, citing a larger patient population and a curative-intent setting aimed at preventing recurrence and preserving long-term survival.
At an illustrative $200,000 course of neoadjuvant treatment, Taylor said the addressable market opportunity would translate to more than $7 billion.
Investigators Discuss Clinical Foundation
Professor Myriam Chalabi of the Netherlands Cancer Institute, an investigator in the upcoming ROBBIN trial, said standard colon cancer treatment has not changed significantly over the past 20 years. She said patients are generally treated with surgery followed by a decision on adjuvant chemotherapy, and that 20% to 40% of patients can still recur despite surgery and chemotherapy.
Chalabi discussed the FOXTROT study, which evaluated neoadjuvant chemotherapy in colon cancer and helped demonstrate feasibility. She also cited her NICHE work, in which neoadjuvant immunotherapy with ipilimumab and nivolumab produced responses in a subset of MSS colon cancer patients. She said the findings supported the hypothesis that treating earlier in the disease course could improve immunotherapy responses.
Dr. Pashtoon Kasi of City of Hope Orange County reviewed the NEST and UNICORN studies of BOT/BAL in the neoadjuvant setting. He said the studies are relevant because they evaluate the combination before surgery while the tumor remains present, within a timeline that fits surgical care.
Kasi said that in MSS tumors in the NEST data, responses included about 59% with at least 50% tumor regression, about 41% with at least 90% tumor regression and about one-third with pathologic complete response. He also said no recurrences had been reported to date across the studies discussed, while noting follow-up remains early.
On safety, Kasi said no surgeries were delayed in the NEST studies. He said one patient in the UNICORN study had surgery delayed by 10 days after a period of hyperthyroidism, and that immune-related adverse events across more than 52 patients were manageable and expected.
Late-Line Programs and Access Questions
During the question-and-answer session, Garo Armen said Agenus would meet its obligations to patients currently enrolled in the BATTMAN study, including providing study drug. He said the company’s decision to prioritize ROBBIN was not driven by outside circumstances, FDA feedback or new BATTMAN data, but by strategic considerations around patient impact and resource allocation.
Armen said the French AAC program in late-stage disease will continue, with the French government paying for eligible French patients. He also said Agenus has instituted a paid named patient program in several countries for patients who can travel and pay out of pocket.
Asked about accelerated approval in late-line disease, Armen said the question remains open and would depend on FDA input, company strategy and financial and personnel resources. O’Day added that real-world outcome data are being collected under the French AAC program, though not with the rigor of a clinical trial.
O’Day also said updated NEST and UNICORN data are under active manuscript review, with publications expected to provide additional clinical and translational information on BOT/BAL.
About Agenus (NASDAQ:AGEN)
Agenus, Inc (NASDAQ:AGEN) is a clinical-stage immuno-oncology company headquartered in Lexington, Massachusetts. The company focuses on the discovery and development of therapies designed to modulate the immune system’s response to cancer. Leveraging proprietary platforms in checkpoint modulation, vaccine technology and adjuvant systems, Agenus aims to deliver combination regimens that enhance antitumor activity across a variety of solid tumors and hematological malignancies.
Agenus’ pipeline includes monoclonal antibodies targeting immune checkpoints, cytokine-based therapeutics and vaccine candidates built on its engineered heat shock protein (HSP) platform.
