Agenus (NASDAQ:AGEN) is concentrating its registration strategy for BOT/BAL on the Phase III ROBBIN trial in neoadjuvant high-risk stage II and III microsatellite-stable (MSS) colon cancer, after ending funding for its BATTMAN study in later-line metastatic disease.
Zack Armen, Agenus’ vice president of corporate development and investor relations, said the company made the decision during July financing discussions, citing the operational and capital demands of conducting multiple global Phase III trials. He said the company believes the earlier-stage setting offers the potential for a more profound patient impact, including reduced use of chemotherapy and radiation, preservation of organs in some rectal cancer cases, and improved event-free survival.
“It is really hard to go stand up a global Phase III trial for any small or mid-size biotech company,” Armen said. “The idea of doing two of those at the same time was a concern around bandwidth and resources.”
Focus shifts to neoadjuvant study
ROBBIN is designed as an 850-patient trial. Armen said Agenus expects to enroll its first patient in the first quarter of 2027, with an interim pathologic-response analysis expected in the fourth quarter of 2027. The analysis will examine the first 100 treated patients, split evenly between the BOT/BAL and control arms.
He emphasized that the interim pathologic-response assessment is not a primary endpoint or a go/no-go decision for the trial. Instead, it is intended to provide an early view of rates of tumor shrinkage, major pathologic response and pathologic complete response.
The company expects an interim event-free-survival analysis at 75% information fraction in the second half of 2029, followed by a final analysis in the second half of 2030. Armen said the company’s financing was structured around certain development milestones. Enrollment of the 60th patient, anticipated in the second quarter of 2027, would trigger a tranche of warrants that could generate $85 million in additional proceeds if fully exercised.
Armen said the study targets a hazard ratio of 0.65, representing at least a 35% improvement in recurrence risk, though he said the company believes it could exceed that target. He also cited chemotherapy de-escalation and maintenance of circulating tumor DNA negativity as secondary or exploratory areas of interest.
Early data inform expectations
Benjamin Schlechter, a senior physician at Dana-Farber, said the biological case for BOT/BAL is strongest in the neoadjuvant setting, although he also sees substantial unmet need among patients with refractory metastatic disease.
Discussing the NEST and UNICORN studies, Schlechter said the reported responses were notable. “They receive six weeks of therapy, and then nearly half of them have no cancer,” he said. “That is a remarkable response.” He cautioned, however, that a major response does not establish that patients have been cured.
Armen said NEST follow-up extending beyond two and three years has shown no disease recurrences among treated patients. He said standard surgery and chemotherapy in this setting are typically associated with recurrence in roughly 25% of patients. Agenus plans to provide further updates from UNICORN in coming weeks and months.
Schlechter said a 2027 pathologic complete response result could help drive interest in ROBBIN enrollment if the response rates hold in a multicenter setting. He suggested enrollment could begin slowly because newly diagnosed patients may prefer immediate surgery, but could accelerate after additional data become available.
Agenus also cited upcoming investigator-sponsored presentations, including NEOASIS data in neoadjuvant colon cancer and agenT-797 combination work. Schlechter said the NEST publication and a potentially similar UNICORN result could be compelling for investigators and patients.
Access programs and metastatic setting
While deprioritizing BATTMAN as a company-funded registration program, Armen said Agenus continues to seek ways for patients with later-line refractory MSS colorectal cancer and other tumors to access BOT/BAL. He said the company has enrolled more than 1,000 patients across later-line metastatic settings and operates compassionate-access programs in more than 30 countries.
According to Armen, France’s AAC program reimburses the therapy for patients with later-line refractory MSS colon and rectal cancer, sarcoma and ovarian cancer. He also said Agenus recently received marketing authorization in Armenia for advanced metastatic MSS colorectal cancer.
Armen described ex-U.S. access and authorization as important validation of patient and physician demand, but not the primary anticipated driver of the company’s opportunity. He said Agenus views the potential value of ROBBIN and other neoadjuvant work as the central long-term opportunity.
Schlechter said investigators were disappointed by the discontinuation of BATTMAN funding, particularly given the needs of refractory-disease patients. Armen acknowledged the decision was difficult and said Agenus is working closely with prospective ROBBIN sites to ensure investigators, surgeons and gastroenterologists are aligned on the study’s approach. He said the company has not encountered significant resistance to ROBBIN because of BATTMAN’s discontinuation.
About Agenus (NASDAQ:AGEN)
Agenus Inc (NASDAQ: AGEN) is a biotechnology company focused on developing immunotherapies for the treatment of cancer. The company’s research programs are designed to activate and strengthen the immune system’s ability to recognize and attack tumors, with an emphasis on therapies that may be used alone or in combination.
Agenus’ pipeline includes botensilimab, an investigational Fc-enhanced CTLA-4 antibody, and balstilimab, an investigational PD-1 inhibitor. The company has studied these therapies in combination across several solid-tumor indications, including colorectal cancer and other advanced cancers.
