Agenus Inc. reported breakthrough clinical results for its botensilimab (BOT) and balstilimab (BAL) combination therapy, demonstrating unprecedented response rates in microsatellite stable (MSS) "cold tumors" that have historically failed to respond to current immuno-oncology treatments. The company presented new data at the American Association for Cancer Research (AACR) Annual Meeting showing robust activity across multiple hard-to-treat cancer types.
Exceptional Response Rates in Colorectal Cancer
The most striking results came from patients with mismatch repair-deficient (dMMR) colorectal cancer, where 100% of patients receiving a higher dose of the BOT/BAL combination achieved pathological complete response (pCR). This represents a significant breakthrough in treating these challenging cancers.
"The growing strength of our BOT/BAL data across multiple hard-to-treat cancers reinforces our conviction in its transformative potential and fuels our unwavering commitment to delivering this combination to patients," said Garo Armen, Ph.D., Chairman and CEO of Agenus.
Pan-Cancer Activity Demonstrated
New data from the investigator-sponsored NEOASIS study, the third clinical trial evaluating BOT/BAL in the neoadjuvant setting, showed the combination can induce pathological responses in patients with solid tumors beyond colorectal cancer, including triple-negative breast cancer (TNBC) and sarcomas. Importantly, no dose-limiting toxicities were observed in the safety run-in portion, and all patients proceeded to their scheduled surgery.
The company also presented new data from the hepatocellular carcinoma (HCC) cohort of its ongoing Phase 1 study. This cohort comprised patients with difficult-to-treat disease who had progressed following standard treatments, including approved immunotherapies. The durable responses and disease control in heavily pretreated HCC patients highlight the strength and differentiation of the BOT/BAL combination.
Mechanism of Action and Clinical Experience
Botensilimab is a human Fc enhanced CTLA-4 blocking 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. The drug augments immune responses by priming and activating T cells, downregulating intratumoral regulatory T cells, activating myeloid cells and inducing long-term memory responses.
Approximately 1,100 patients have been treated with botensilimab in phase 1 and phase 2 clinical trials. Botensilimab alone, or in combination with balstilimab, has shown clinical responses across nine metastatic, late-line cancers.
Balstilimab is a novel, fully human monoclonal immunoglobulin G4 (IgG4) designed to block PD-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 profile in several tumor types.
Strategic Leadership Addition
To accelerate the program toward regulatory milestones, Agenus appointed Dr. Richard Goldberg, an internationally recognized leader in gastrointestinal cancer treatment and research, as Chief Development Officer. Dr. Goldberg stepped out of early retirement to join the company and will lead efforts as Agenus prepares to re-engage global regulatory authorities with expanded data and longer-term follow-up in metastatic colorectal cancer.
Financial Position and Operational Efficiency
For the first quarter ended March 31, 2025, Agenus recognized revenue of $24.1 million and incurred a net loss of $26.4 million, or $1.03 per share. This compares to revenue of $28.0 million and a net loss of $63.5 million or $3.04 per share for the same period in 2024. Revenue primarily includes non-cash royalty revenue.
The company ended Q1 2025 with a consolidated cash balance of $18.5 million compared to $40.4 million on December 31, 2024. Cash used in operations for the first quarter was $25.6 million, reduced from $38.2 million for the same period in 2024.
Agenus is on track to reduce its annualized operating cash burn below $50 million starting in the second half of 2025, supported by recent cost optimization measures. The company is in the final stages of an important collaboration which will result in substantial cash infusion.
