Botensilimab/Balstilimab Breakthrough Data Presented at ASCO-GI Shows Unprecedented Tumor Shrinkage and Robust Biomarker Response in Prevalent Colorectal Cancer Population

Agenus Inc. (Nasdaq: AGEN), a leader in developing immunological cancer treatments, today announced results from the NEST-1 study, an investigator-sponsored trial (IST) evaluating the combination of botensilimab and balstilimab (BOT/BAL) in the neoadjuvant setting for colorectal cancer (CRC), both those with Microsatellite Stable (MSS) CRC and Microsatellite Instability High (MSI-H) CRC. Dr. Pashtoon Kasi, M.D., Director of Colon Cancer Research at Weill-Cornell Medicine, presented these findings at the ASCO-GI conference.

"BOT/BAL's potential impact on colorectal cancer is groundbreaking. The study's findings, particularly the significant tumor regression after only a single dose of BOT and two doses of BAL, and the complete elimination of ctDNA in 100% of patients tested, offer a potentially transformative treatment approach for CRC patients diagnosed with early stage and locally advanced colon and rectal cancers. These results hold great promise for patients and providers as a framework for reduced reliance on chemotherapy and/or surgical resection," said Dr. Pashtoon Kasi, M.D., Director of Colon Cancer Research at Weill-Cornell Medicine and lead investigator of the NICHE-1 study.

Study Highlights:

• Treatment Protocol: Patients received a single dose of BOT and two doses of BAL between diagnosis and surgery, which was approximately a four-week period.
• Impressive Pathologic Response: Tumor shrinkage of ≥50% was observed in 67.5% of patients in the Microsatellite Stable (MSS) CRC cohort and 100% in the Microsatellite Instability-High (MSI-High) CRC cohort.
• Surgery Without Delays: Treatment with BOT/BAL did not cause any postponements in surgical procedures, with only two instances of Grade 3 Treatment-Related Adverse Events (TRAEs) observed.
• BOT/BAL Eliminates Circulating Tumor DNA (ctDNA): patients in the NICHE-1 study were tested for ctDNA, a biomarker closely associated with long-term Disease-Free Survival (DFS).
• In a separate, independent observational study of 1,792 patients (NCT04264702; https://meetings.asco.org/abstracts-presentations/228848), also led by Dr. Kasi and presented at the ASCO-GI meeting on January 20^th, showed a correlation between ctDNA clearance and improved disease-free survival (DFS) rates. Patients who remained ctDNA negative post-treatment exhibited better 2-year DFS as compared to ctDNA-positive patients.

Dr. Steven O’Day, Chief Medical Officer of Agenus, stated, “The NEST-1 trial results are remarkable. Neoadjuvant BOT/BAL in both MSS and MSI-H CRC resulted in marked tumor regression and robust immune cell infiltration in a very short interval. These results in MSS CRC (90% of all CRC) are particularly compelling and may lead to an unprecedented shift away from invasive and morbid standard treatments in the future.”