botensilimab (AGEN1181) / Agenus - LARVOL DELTA

Results from a phase 1 study of botensilimab and balstilimab in treatment refractory hepatocellular carcinoma (AACR 2025) - P1 | "Pts received a median of 2 prior lines of therapy (range 1–7); all had received prior PD-(L)1 as part of combination therapy (58% atezolizumab/bevacizumab [atezo/bev]) and 63% received prior receptor tyrosine kinase inhibitors...All 3 responders received prior atezo/bev; 1 also received lenvatinib; another also received sorafenib and a MER/AXL-targeted therapy (clinical trial)...The safety profile was manageable and consistent with other disease cohorts treated with BOT/BAL. These results support further investigation."

Late-breaking abstract • P1 data • Hepatocellular Cancer • Oncology • Solid Tumor • AXL

Agenus Announces New Data from Expanded MSS Metastatic Colorectal Cancer Cohort to be Presented at ESMO GI 2025 (Businesswire) - "Agenus Inc...today announced new data from its ongoing Phase 1 trial evaluating botensilimab and balstilimab (BOT/BAL) in patients with microsatellite stable (MSS) metastatic colorectal cancer (mCRC) at the 2025 European Society for Medical Oncology (ESMO) Gastrointestinal Cancers Congress in Barcelona, Spain. A poster presentation will feature updated findings from an expanded cohort of 123 patients, incorporating additional participants and extended follow-up to further assess clinical activity of the combination, including durability of response and overall survival."

P1 data • Colorectal Cancer

C-800-25: A Study of Botensilimab and Balstilimab for the Treatment of Colorectal Cancer (clinicaltrials.gov) - P2 | N=234 | Active, not recruiting | Sponsor: Agenus Inc. | Trial completion date: Jul 2025 ➔ Sep 2029 | Trial primary completion date: Feb 2025 ➔ Sep 2027

Monotherapy • Trial completion date • Trial primary completion date • Colorectal Cancer • Oncology • Solid Tumor • BRAF • EGFR • MSI

Mutant KRAS peptide vaccine combined with ipilimumab/nivolumab in advanced mismatch repair proficient/microsatellite stable (MMRp/MSS) colorectal cancer: Preliminary analysis from a phase I study (AACR 2025) - P1 | "Key inclusion criteria included tumor expression of a KRAS mutation included in mKRAS-VAX and prior 5-fluorouracil, oxaliplatin, and irinotecan exposure. mKRAS-VAX and ipi/nivo is well-tolerated and induced mKRAS-specific T-cell responses. Moreover, this strategy resulted in meaningful clinical responses in chemorefractory metastatic mKRAS MMRp/MSS CRC with OS that was provocative. Ongoing studies of the T cell repertoire in blood and tumor tissue will be used to identify biomarkers that predict response to mKRAS-targeted immunotherapy."

IO biomarker • Metastases • Mismatch repair • P1 data • pMMR • Colorectal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • IFNG • KRAS

Agenus Reports Q1 2025 Financial Results and Key Business Updates (Agenus Inc. Press Release) - "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 enabling the company to direct resources toward ensuring the potential of BOT/BAL is realized. The company is in final stages of an important collaboration which will result in substantial cash infusion."

Commercial • dMMR • MSI-H • Colorectal Cancer • Hepatocellular Cancer • Microsatellite Instability • Sarcoma • Triple Negative Breast Cancer

Botensilimab Plus Balstilimab Elicits Durable Responses in Treatment-Refractory HCC (OncLive) - "'Botensilimab/balstilimab demonstrated durable responses and prolonged stable disease in patients with treatment-refractory HCC, with a median of two prior lines of therapy and progressed on or after I-O, including patients who received prior atezolizumab [Tecentriq]/bevacizumab [Avastin],' Anthony B. El-Khoueiry, MD...and colleagues wrote in a poster of the data. 'The DCR and survival data provide early evidence of antitumor activity in the setting of prior I-O–based therapy.'"

Media quote

Evaluating Efficacy of Fc-enhanced CTLA-4 Inhibitor Botensilimab, Bastilimab with or without CXCR4 Inhibitor (BL-8040) in an Orthotopic Murine Model (ESMO-GI 2025) - No abstract available

Preclinical • CXCR4

Agenus’ BOT/BAL Neoadjuvant Pan-Cancer Data from the NEOASIS Study Presented in an Oral Session at AACR (Businesswire) - P2/3 | N=92 | NEOASIS (NCT06279130) | "The safety run-in enrolled patients with non-metastatic solid tumors, divided into two cohorts of 10 patients each: dMMR/MSI-H and pMMR/MSS....Results: (i) dMMR/MSI-H Cohort (9 colorectal, 1 duodenal cancer): Pathological response rate: 90%; Major pathological response (MPR): 80%; Pathological complete response (pCR): 70%; (ii) pMMR/MSS Cohort (6 triple-negative breast cancer, 2 ER+ breast cancer, 1 merkel cell carcinoma, 1 sarcoma): Pathological response rate: 80%; Major pathological response (MPR): 70%; Pathological complete response (pCR): 20%; Triple-negative breast cancer subgroup (n=6): 63% achieved MPR."

dMMR • MSI-H • P2 data • Colorectal Cancer • Estrogen Receptor Positive Breast Cancer • Merkel Cell Carcinoma • Microsatellite Instability • Sarcoma • Triple Negative Breast Cancer

Agenus’ BOT/BAL Data in Pretreated Liver Cancer Presented at AACR 2025 (Businesswire) - P1 | N=499 | NCT03860272 | Sponsor: Agenus Inc. | "Phase 1 Study Overview: BOT/BAL in Treatment-Refractory Hepatocellular Carcinoma (NCT03860272)...The HCC cohort enrolled 19 patients (18 evaluable for efficacy) with treatment-refractory metastatic HCC. Patients received a median of two prior therapies, and progressed on or following anti-PD(L)-1. Patients were administered BOT (1 or 2 mg/kg) in combination with BAL (3 mg/kg)....Key Results: Overall response rate: 17%; Stable disease rate: 56%; Disease control rate: 72%; Median progression-free survival: 4.4 months; Median overall survival: 12.3 months....The safety profile of the BOT/BAL combination remained consistent with previous cohorts and was manageable."

P1 data • Hepatocellular Cancer

An open-label, phase 1 trial with expansion cohort of botensilimab (AGEN1181) + balstilimab (AGEN2034) + nab-paclitaxel + gemcitabine + cisplatin + chloroquine + celecoxib in adult patients with previously untreated metastatic pancreatic cancer. (ASCO 2025) - P1 | "Clinical Trial Registration Number: NCT06076837 The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Clinical • Metastases • P1 data • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor

Monitoring botensilimab- and balstilimab-induced T-cell dynamics in refractory mismatch repair proficient metastatic colorectal cancer. (ASCO 2025) - "The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Metastases • Mismatch repair • pMMR • Colorectal Cancer • Oncology • Solid Tumor

Study of AGEN1571 in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=22 | Completed | Sponsor: Agenus Inc. | Active, not recruiting ➔ Completed | Trial completion date: Jan 2027 ➔ Dec 2024 | Trial primary completion date: Jan 2027 ➔ Dec 2024

Trial completion • Trial completion date • Trial primary completion date • Solid Tumor

A phase 2 study of SR-8541A in combination with botensilimab and balstilimab in subjects with refractory metastatic microsatellite stable colorectal cancer (MSS-CRC). (ASCO 2025) - P2 | "Clinical Trial Registration Number: NCT06589440 The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Clinical • Combination therapy • Metastases • P2 data • Colorectal Cancer • Oncology • Solid Tumor

Agenus Announces Botensilimab and Balstilimab Presentations at ASCO 2025 (Businesswire) - "Agenus Inc...announced three upcoming presentations at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, taking place May 30 – June 3 in Chicago, Illinois. A poster presentation will highlight new translational data monitoring induced T-cell dynamics from the botensilimab and balstilimab (BOT/BAL) program in mismatch repair–proficient (pMMR)/microsatellite stable (MSS) metastatic colorectal cancer (mCRC). In addition, two trials-in-progress presentations will showcase the design and scientific rationale of ongoing clinical studies evaluating botensilimab-based combinations in advanced pancreatic cancer."

Clinical data • pMMR • Trial status • Colorectal Adenocarcinoma • Pancreatic Cancer

A phase 2 study of SR-8541A in combination with botensilimab and balstilimab in subjects with refractory metastatic microsatellite stable colorectal cancer (MSS-CRC) (AACR 2025) - P1, P2 | "SR-8541A is administered orally twice daily (BID) in 28-day cycles. Blood samples are being collected for PK assessment, target engagement, and biomarker assessment."

Clinical • Combination therapy • IO biomarker • Metastases • P2 data • Colorectal Cancer • Microsatellite Instability • Oncology • Solid Tumor • CGAS • CTLA4 • ENPP1 • MSI • STING

A phase 2 study of botensilimab and AGEN1423, an anti-CD73-TGFβ-trap bifunctional antibody, with or without chemotherapy in subjects with advanced pancreatic cancer. (ASCO 2025) - P2 | "Clinical Trial Registration Number: NCT05632328 The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Clinical • Metastases • P2 data • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor • TGFB1

Botensilimab plus balstilimab in an expanded cohort of 123 patients with metastatic microsatellite stable colorectal cancer and no active liver metastases (ESMO-GI 2025) - No abstract available

Clinical • Metastases • Colorectal Cancer • Oncology • Solid Tumor

Neoadjuvant botensilimab plus balstilimab in MMR proficient and deficient early stage cancers: First results of the pan-cancer NEOASIS study (AACR 2025) - "Data of the safety run-in of 20 pts show that neoadjuvant bot/bal was safe and did not lead to surgical delays. In addition, the observed pathological responses are encouraging and suggest a potential for neoadjuvant immunotherapy using bot/bal across tumor types, including pMMR BC and sarcoma. Accrual in efficacy baskets for both dMMR and pMMR tumors is currently ongoing at the bot 50mg dose level."

Clinical • Pan tumor • Breast Cancer • Colorectal Cancer • Merkel Cell Carcinoma • Non-melanoma Skin Cancer • Oncology • Sarcoma • Skin Cancer • Small Intestinal Carcinoma • Solid Tumor • Triple Negative Breast Cancer

A phase Ib study of a pooled synthetic long peptide mutant KRAS vaccine combined with balstilimab/botensilimab in metastatic pancreatic cancer and metastatic MMR-proficient colorectal cancer in the maintenance setting. (ASCO 2025) - P1 | "Clinical Trial Registration Number: NCT06411691 The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Clinical • Metastases • P1 data • Colorectal Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor • KRAS

Doxorubicin Plus Dual Checkpoint Blockade for Soft Tissue Sarcomas (clinicaltrials.gov) - P2 | N=65 | Recruiting | Sponsor: University of Colorado, Denver | N=28 ➔ 65

Checkpoint inhibition • Enrollment change • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

KRAS-Targeted Vaccine Combined With Balstilimab and Botensilimab for Patients With Stage IV MMR-p Colorectal Cancer and Pancreatic Ductal Cancer (clinicaltrials.gov) - P1 | N=54 | Recruiting | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Nov 2027 ➔ Nov 2028 | Trial primary completion date: Nov 2027 ➔ Nov 2028

Trial completion date • Trial primary completion date • Colorectal Cancer • Hepatology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • KRAS

Agenus to Present New BOT/BAL Data in Two Presentations at AACR 2025 (Businesswire) - "Agenus...announced two upcoming presentations at the American Association for Cancer Research (AACR) Annual Meeting....The presentations continue to build momentum for Agenus’ neoadjuvant immunotherapy program with botensilimab and balstilimab (BOT/BAL), including an oral presentation of the initial results from the NEOASIS trial in solid tumors and a poster featuring new data from the advanced hepatocellular carcinoma (HCC) cohort of a Phase 1 study evaluating BOT/BAL in patients with advanced solid tumors."

Clinical data • Hepatocellular Cancer

Platform Study of Immunotherapy Combinations in Colorectal Cancer Liver Metastases (clinicaltrials.gov) - P2 | N=24 | Recruiting | Sponsor: Weill Medical College of Cornell University | Trial primary completion date: Sep 2025 ➔ Sep 2026

Trial primary completion date • Colorectal Cancer • Hepatology • Oncology • Solid Tumor

Agenus Reports Q4 and Year-End 2024 Results; Strategic Operational Improvements and Significant Cost Reductions Enhance Sustainability of Promising BOT/BAL Program (Businesswire) - "'In line with our strategic objectives, we significantly reduced our annualized operational burn rate. We anticipate further reducing our annual burn to an annualized rate of approximately $50 million by mid-2025 through the externalization of development costs associated with BOT/BAL, monetization of our CMC assets, and other reductions in operating expenses'."

Commercial • Colorectal Cancer

A Study of Botensilimab (AGEN1181) for the Treatment of Advanced Melanoma (clinicaltrials.gov) - P2 | N=174 | Active, not recruiting | Sponsor: Agenus Inc. | Trial completion date: May 2028 ➔ Feb 2028 | Trial primary completion date: May 2028 ➔ Feb 2028

Checkpoint inhibition • Trial completion date • Trial primary completion date • Cutaneous Melanoma • Melanoma • Oncology • Solid Tumor • BRAF