In July 2024, Amalya Sargsyan, MD, VP, Research & Intelligence, covered the most promising cancer drugs of the year for OncoDaily in her feature “10 Most Promising Cancer Drugs in 2024: What Patients Need to Know,” naming botensilimab among the top 10 therapies to watch. At the time, the drug was showing early signs of activity in hard-to-treat colorectal cancer. Its combination with balstilimab — now known as BOT/BAL — has since emerged as one of the most closely watched regimens in microsatellite-stable (MSS) colorectal cancer, one of the most immunotherapy-resistant malignancies.
Two years and a string of clinical milestones later, that promise has been backed by a private placement of up to $340 million. The deal includes $85 million upfront, with up to $255 million more upon the full exercise of purchase warrants, to fund a registrational Phase 3 trial.
Two Years of Clinical Progress
The combination targets two complementary immune checkpoints. Botensilimab (BOT) is an Fc-enhanced anti-CTLA-4 antibody engineered to go beyond conventional CTLA-4 blockade — it primes and activates T cells, suppresses regulatory T cells within the tumor microenvironment, engages myeloid cell populations, and promotes durable immune memory. These mechanisms are designed to convert immunologically “cold” tumors into environments capable of mounting an effective antitumor response.
Balstilimab (BAL) is a fully human anti-PD-1 antibody that blocks PD-1’s interaction with its ligands PD-L1 and PD-L2, releasing T cells from a key suppressive brake. Together, BOT provides immune priming and activation while BAL sustains the unleashed immune response.
ESMO GI 2025: Durable Survival in Refractory MSS mCRC
At ESMO GI 2025, Dr. Benjamin Schlechter of Dana-Farber Cancer Institute presented updated results from the fully enrolled Phase 1b C-800-01 cohort of 123 heavily pretreated MSS mCRC patients without active liver metastases. The median number of prior treatment lines was 3, with 67% having received at least 3 prior regimens.
The combination achieved a 20% objective response rate, including 3 complete responses, with a median duration of response of 16.6 months. Median overall survival reached 20.9 months, with 57% of patients alive at 18 months. Notably, 20% of patients were alive and off treatment at data cutoff, suggesting treatment-free survival. There were no treatment-related deaths.
France Grants Compassionate Access
In September 2025, France granted reimbursed compassionate access for BOT/BAL in refractory MSS mCRC. The French National Agency for Medicines and Health Products Safety (ANSM) approved hospital use through the national Accès Compassionnel program, with treatment fully reimbursed by Assurance Maladie for eligible patients with MSS status and no active liver metastases — a regulatory milestone signaling growing institutional confidence in the combination.
AACR 2026: First-Line Activity in BBOpCo
At AACR 2026, Nicholas DeVito of Duke University presented preliminary results from the BBOpCo study evaluating first-line BOT/BAL in 15 previously untreated MSS CRC patients without liver, bone, or brain metastases. The combination achieved a 71% disease control rate, including one confirmed immune partial response in a patient with a tumor mutational burden of just 1 mut/Mb — underscoring BOT/BAL’s ability to generate immune responses even in the coldest MSS tumors.
A key finding was the median freedom from crossover to chemotherapy of 8.7 months, and among patients who did eventually transition to standard chemotherapy, responsiveness to subsequent treatment was maintained. No Grade 4 toxicities or treatment-related deaths were reported.
BATTMAN Launches — Then a Strategic Pivot
In April 2026, the Phase 3 BATTMAN trial — evaluating BOT/BAL versus best supportive care in late-line metastatic MSS CRC — enrolled its first patient across a global network of more than 100 sites, led by the Canadian Cancer Trials Group (CCTG) with participation from GI Cancer Trials in Australia and France’s PRODIGE consortium. But just months later, as part of its ROBBIN strategy, Agenus announced it would discontinue financial support for BATTMAN to concentrate its resources on the neoadjuvant setting, where the company sees the greatest opportunity for curative-intent impact.
Agenus said it would honor its obligations to patients currently receiving treatment and work closely with CCTG and participating investigators to manage the transition.
ESMO GI 2026: Three-Year Survival Plateau
By ESMO GI 2026, extended follow-up of the same Phase 1b cohort — now with a median follow-up of 34.8 months — confirmed a 3-year overall survival rate of 33% and a confirmed objective response rate of 21%. Median duration of response was still not reached. Efficacy was consistent even in patients previously exposed to late-line agents such as regorafenib, fruquintinib, or trifluridine/tipiracil with or without bevacizumab, with a 22% response rate and 30% three-year survival in that subgroup. The findings point to a durable survival plateau in MSS mCRC — a disease where such a plateau was previously unheard of with immunotherapy.
$340 Million and the ROBBIN Trial
On July 13, 2026, Agenus announced an oversubscribed private placement expected to generate up to $340 million — $85 million upfront, with up to $255 million through warrant exercise. The financing, led by Commodore Capital with participation from RA Capital Management, TCGX, Invus, and Ligand Pharmaceuticals, is structured specifically to fund ROBBIN.
ROBBIN is a planned 850-patient, randomized, global Phase 3 trial evaluating neoadjuvant BOT/BAL in previously untreated high-risk Stage II and Stage III MSS colon cancer — a population of approximately 38,000 patients per year in the US, with no new curative-intent therapy approved in over two decades.
The trial builds on Phase 2 findings from the NEST and UNICORN studies, which reported pathologic response rates of 60–70%, pathologic complete responses in approximately 30% of patients, and no recurrences at median follow-up of 9 to 18 months.
First patient dosing is expected in Q1 2027, with interim pathologic response data anticipated in the second half of 2027.
From Promise to Proof
When Amalya Sargsyan selected botensilimab for OncoDaily’s 2024 list, the question was whether its engineered design could convert cold tumors into responsive ones. The accumulating evidence, from Phase 1b through Phase 2, from metastatic to neoadjuvant settings, from late-line to first-line — has steadily built the case. ROBBIN is now positioned to answer that question definitively, in a registrational trial, for MSS colon cancer patients being treated with curative intent.
The full announcement is available from Agenus Inc.