Opinion

May 15, 2025, 17:00

Agenus Bets Big on Botensilimab

In early 2025, Agenus Inc.—long known for its immuno-oncology ambitions—delivered a pivotal update. At its Q1 earnings call, the company unveiled striking new clinical results, a strategic leadership pivot, and a sharpened focus on its flagship immunotherapy duo—botensilimab (BOT) and balstilimab (BAL). This wasn’t a company reporting progress. It was a company signaling transformation.

At the American Association for Cancer Research (AACR) Annual Meeting, BOT/BAL emerged as one of the meeting’s most closely watched combinations. In the NEOASIS trial, BOT/BAL achieved 70% major pathological response (MPR) in dMMR colorectal tumors and 20% in MSS tumors, where immunotherapy has historically failed. In advanced hepatocellular carcinoma (HCC), the combo delivered a 17% overall response rate and 72% disease control rate, including patients previously unresponsive to checkpoint inhibitors. Neoadjuvant trials like NEST and UNICORN reinforced the impact, with complete ctDNA clearance, high pCR rates, and no delays to surgery.

To steer this forward, Agenus appointed Dr. Richard Goldberg as Chief Development Officer. A globally respected GI oncology leader, Goldberg brings experience from The Ohio State University and UNC Lineberger Comprehensive Cancer Center.

“Patients and their families clamor daily for better treatments, they want more time, better time, and ultimately curative interventions. This combination is among the most promising I’ve seen”

richard goldberg agenus

His arrival doesn’t just add expertise—it sends a message. Agenus is preparing for the next regulatory leap, and it’s doing so with veteran leadership at the helm.

On the financial front, Agenus is demonstrating rare discipline for a pre-commercial biotech. In Q1 2025, the company cut its net loss by nearly 60%, bringing it down to $26.4 million, and slashed operating cash burn to $25.6 million. With a goal to reduce annualized expenses below $50 million by midyear and a capital infusion in the final stages, Agenus is realigning its entire business around the promise of BOT/BAL.

Regulatory tides may also be shifting in its favor. Under FDA Commissioner Dr. Marty Makary, the agency embraces flexibility, particularly for therapies that show real promise in high-need indications. For a combination like BOT/BAL, which has demonstrated responses in microsatellite-stable colorectal cancer (MSS CRC)—a setting long resistant to immunotherapy—this shift could prove decisive.

The markets took notice. Following the Q1 earnings and data announcements, Agenus shares jumped 23% in a single session—the strongest signal yet that investors see more than incremental progress. They see potential for a biotech revival.

10 most promising

In 2024, OncoDaily named botensilimab among the “10 Most Promising Cancer Drugs Not Yet Approved.” With several of its peers now FDA-approved in early 2025, one question rises above the rest:

Will BOT be the next?

The question now is whether these aligned forces—compelling science, credible leadership, financial discipline, and a more receptive FDA—are enough to turn momentum into approval. For Agenus, 2025 may not just be a comeback year. It could be the beginning of a new era.