Agenus (NASDAQ:AGEN) used its March stakeholder webcast to highlight progress for its investigational immunotherapy combination of botensilimab and balstilimab (bot/bal), emphasizing efforts to broaden immunotherapy’s reach into “cold” tumors such as microsatellite stable (MSS) metastatic colorectal cancer (mCRC), where conventional checkpoint inhibitors have historically shown limited benefit.
Company frames MSS colorectal cancer as a key unmet need
Chief Communications Officer Stefanie Perna-Nacar opened the webcast by pointing to recently published American Cancer Society data showing colorectal cancer is now the leading cause of cancer-related death in people under 50 in the U.S., with mortality continuing to worsen in younger adults. Perna-Nacar said Agenus is focused on MSS tumors, which she said account for approximately 95% of metastatic colorectal cancer and a substantial portion of solid tumors more broadly.
Clinical leaders describe a broad dataset and durability signals
Chief Medical Officer Dr. Steven O’Day, who described his prior clinical experience during the first wave of checkpoint inhibitors in melanoma, said he began seeing “very similar patterns to melanoma” in early bot/bal trials, including in tumor types he described as historically resistant to checkpoint blockade such as MSS colorectal cancer, refractory ovarian cancer, and sarcomas.
Armen said the bot/bal program now includes more than 1,200 patients treated across nine tumor types. O’Day emphasized what he described as consistency and reproducibility across datasets and tumor types, adding that the company is seeing activity translate into long-term survival, including treatment-free survival. He referenced “flattening of OS curves over time” as part of what he finds compelling in the emerging data.
Discussing mechanism, O’Day said botensilimab’s engineered Fc is intended to strengthen the interaction between antigen-presenting cells and T cells, expanding the T-cell repertoire and enabling recognition of tumors that are poorly immunogenic. He described balstilimab (a PD-1) as supporting the expanded T cells and helping prevent exhaustion, calling the combination “essential” for cold tumors.
BATMAN phase III trial positioned as registrational pathway
O’Day said Agenus has aligned key elements of its colorectal program with regulators, including “contribution of components, single agent activity, and dose selection,” and has opened its phase III BATMAN trial. He described BATMAN as a randomized global phase III study in refractory MSS colorectal cancer, including both liver metastasis and non-liver metastasis populations, with survival as the endpoint.
O’Day said the trial is powered to address both subgroups. While he acknowledged the company’s early signal appeared stronger in patients without active liver metastases, he said broader data, including a pan-tumor dataset, showed RECIST responses in patients with active liver metastases. He also said that in a small active liver metastasis group treated in phase I, the company observed disease stabilization and some tumor shrinkage that did not meet RECIST response criteria, while median survival outperformed historical controls.
Neoadjuvant data and a potential future pivotal study
Beyond late-line metastatic disease, O’Day pointed to early-stage colorectal cancer opportunities, referencing the NEST (U.S.) and UNICORN (Italy) neoadjuvant trials. He said a limited course of therapy—“one dose of bot and 2-3 doses of bal” over 6–8 weeks followed by surgery—resulted in complete or near-complete responses in approximately 40% of patients in 4–8 weeks. He said Agenus hopes to publish these results and suggested they could support a de-risked randomized phase III effort in colon cancer with event-free survival (EFS) as an endpoint.
During Q&A, O’Day said the company continues to monitor maturing single-arm phase I/II data and intends to engage U.S. and European regulators about whether the evolving dataset could support an accelerated pathway, while BATMAN accrues as a supportive phase III study for full approval.
Access programs and early revenue discussed alongside operational readiness
Armen said Agenus ended its compassionate use program due to an “explosion of requests” that became untenable given administrative and product costs. In its place, he highlighted France’s AAC program, which he said provides fully reimbursed access for eligible patients with colon cancer, sarcoma, and ovarian cancer. Armen also described a paid named patient program in countries that allow it, including the U.K., Switzerland, Brazil, and Argentina, where patients can obtain treatment if physicians request it and patients pay out of pocket.
Armen said Agenus had received inquiries from 30 countries, totaling 270 inquiries through the end of March. He added that the company has recently formalized a medical education and medical affairs function, which he said will both educate physicians and collect real-world data from AAC and named patient use.
Chief Commercial Officer Dr. Robin Taylor said the French AAC and named patient programs generated $3.2 million in realized revenues in the fourth quarter of last year. Taylor said expanded physician experience and the collection of real-world evidence could support future commercialization, including discussions with payers, and help clinicians learn best practices for managing patients.
In closing remarks, Armen addressed what he called a disconnect between the company’s progress and its market valuation, citing the capital required to move through approval and commercialization. He said the company has taken steps to strengthen operations, expand access programs, advance BATMAN, and pursue regulatory paths, while also noting that Agenus has other molecules “put on the shelf” until additional resources are available.
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.
