Median Overall Survival of 20.9 Months for Patients Without Active Liver Metastases Surpasses the Recently Reported 12.9-Month Benchmark with Standard of Care in this Population

Immuno-oncology leader, Agenus (Nasdaq: AGEN), shared promising data today from its Phase 1b trial on the botensilimab and balstilimab combination at a late-breaking session at the 2023 ESMO World Congress on Gastrointestinal Cancer (ESMO GI). The new data show substantial survival benefits and long-lasting responses for patients with non-MSI-H (microsatellite stable or non-microsatellite instability-high) metastatic colorectal cancer previously resistant to chemotherapy and/or immunotherapy.

“The data from our expanded cohort demonstrate remarkable median overall survival and sustained responses in heavily pre-treated patients that historically haven’t responded to immunotherapy. These findings provide evidence of the benefit of botensilimab/balstilimab in metastatic colorectal cancer, the second leading cause of cancer death in the U.S.,” said Dr. Steven O’Day, Chief Medical Officer at Agenus. “Our clinical research has shown confirmed responses in 8 other refractory tumor types, indicating the potential to transform clinical practice and patient outcomes for multiple challenging cancers.”

Dr. Andrea Bullock, Assistant Professor of Medicine, Harvard Medical School, and study investigator, commented, "The new survival data underscore the potential of the botensilimab/balstilimab combination as an important treatment option for patients with non-MSI-H colorectal cancer. The patients in our study face one of the most challenging cancers to treat and represent the largest patient population with colorectal cancer where only a quarter of patients survive beyond one year with standard of care therapy. Botensilimab plus balstilimab continues to show deep and durable responses with 69% of objective responses still ongoing at the data cutoff."

Agenus is planning to submit its first Biologics License Application to the U.S. Food & Drug Administration (FDA) for patients with non-MSI-H metastatic colorectal cancer. The ongoing global randomized phase 2 trial for patients with non-active liver metastases has been granted Fast Track Designation from the FDA. Additionally, global randomized Phase 2 trials for the botensilimab/balstilimab combination in melanoma and botensilimab/chemotherapy in pancreatic cancer are underway, with plans to initiate Phase 3 studies in colorectal and non-small cell lung cancer (NSCLC).

Study Design:

The study enrolled 101 patients with refractory non-MSI-H metastatic colorectal cancer who were administered botensilimab (either 1 or 2 mg/kg every six weeks) and balstilimab (3 mg/kg every two weeks).

The patients had a median of four prior therapy lines, with 25% having failed previous immunotherapy.

Efficacy was evaluated in 87 patients who had undergone at least one six-week post-baseline imaging scan. Of these, 69 patients had no active liver metastases, defined as patients with no history of liver metastases or those with metastases that were treated or ablated without recurrence.

Half of the patients treated had poor-prognostic metastatic sites beyond the liver, such as bone and soft tissue.

Survival:

Patients without active liver metastases had a 12-month overall survival (OS) estimate of 74% and a median overall survival (mOS) of 20.9 months, surpassing the recently reported 12.9-month benchmark with standard of care.

Patients with active liver metastases had a 12-month OS estimate of 30% and a mOS of 8.7 months, surpassing the recently reported 5.9-month benchmark with standard of care. The botensilimab/balstilimab combination showed a survival benefit, regardless of RECIST 1.1 responses.

mOS estimates for patients, categorized by liver status, were comparable between the efficacy evaluable and the intent-to-treat populations.

Objective Responses:

Evaluable patients without active liver metastases showed a confirmed objective response rate of 23% and a disease control rate of 80%, significantly higher than the reported response rate of 3% with standard of care.

The responses were durable, with 69% of objective responses ongoing at data cutoff. Response durations ranged from 1.4+ months in recently treated patients to over 24.3+ months.

Tolerability:

The botensilimab/balstilimab combination demonstrated a manageable safety profile, with no new safety concerns emerging.

Presentation Details:

Abstract Title: Results from an expanded phase 1 trial of botensilimab, a multifunctional anti-CTLA-4, plus balstilimab (anti-PD-1) for metastatic heavily pretreated microsatellite stable colorectal cancer (NCT03860272)

Abstract Number: LBA-4

Presenting Author: Andrea J. Bullock, MD, MPH, Assistant Professor of Medicine, Division of Medical Oncology, Beth Israel Deaconess Medical Center

Session XVIII: Immune Mechanisms and Microbiome in GI Tumors

Session Time: 6/30/2023, 5:15pm - 6:30pm CEST

Presentation Date and Time: 6/30/2023, 6:00pm – 6:10pm CEST

The presentation can be accessed in the publications section of our website at https://agenusbio.com/publications/.

References:

Grothey et. al. "Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial." Lancet 2013, 381(9863): 303-12

Mayer et. al. "Randomized trial of TAS-102 for refractory metastatic colorectal cancer." NEJM 2015, 372(20): 1909-19

Cohen et al. "Prognostic value of liver metastases in colorectal cancer treated by systemic therapy: An ARCAD pooled analysis." ASCO Annual Meeting 2023, Abstract 3554

About Botensilimab

Botensilimab, an investigational multifunctional CTLA-4 antibody, is designed to extend immunotherapy benefits to "cold" tumors, which have not historically responded to standard of care or investigational therapies. Besides binding to the CTLA-4 receptor, its Fc-enhanced structure induces a memory immune response, downregulates regulatory T cells, and activates T cells, thereby enhancing immune responses. In a Phase 1b clinical study involving over 500 patients, botensilimab has shown clinical responses in 9 solid tumor cancers, either alone or in combination with Agenus’ PD-1 antibody, balstilimab. For more information about botensilimab trials, visit www.clinicaltrials.gov with the identifiers NCT05608044, NCT05630183, and NCT05529316.

About Agenus

Agenus is a leading immuno-oncology company targeting cancer and infectious diseases with a comprehensive pipeline of immunological agents. The Company’s mission is to expand patient populations benefiting from cancer immunotherapy through combination approaches, using a broad repertoire of antibody therapeutics, adoptive cell therapies (through MiNK Therapeutics), and adjuvants (through SaponiQx). Agenus is headquartered in Lexington, MA. For more information, visit www.agenusbio.com or follow us on LinkedIn and Twitter @agenus_bio.

Forward-Looking Statements

This press release contains forward-looking statements under the safe harbor provisions of federal securities laws. These include statements related to botensilimab and balstilimab’s use, such as anticipated therapeutic benefit, efficacy, mechanism of action, potency, durability, and safety profile of the Company's therapeutic candidates. Any statements containing "may," "believes," "expects," "anticipates," "hopes," "intends," "plans," "forecasts," "estimates," "will," “establish,” “potential,” “superiority,” “best in class,” and similar expressions signify forward-looking statements. Actual results could differ materially due to risks and uncertainties, including those described under the Risk Factors section in our most recent Quarterly Report on Form 10-Q or Annual Report on Form 10-K filed with the Securities and Exchange Commission. Agenus urges investors not to place significant reliance on the forward-looking statements in this release. These statements only reflect the views as of the date of this press release, and Agenus undertakes no obligation to update or revise the statements, other than to the extent required by law. All forward-looking statements are expressly qualified in their entirety by this cautionary statement.

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