Significant Tumor Reductions in Neoadjuvant MSS Colon Cancer Patients Treated with Botensilimab/Balstilimab Presented at ESMO GI Conference

Rhea-AI Summary

Agenus Inc. announced promising results from a trial of botensilimab and balstilimab (BOT/BAL) in colon cancer patients at the 2024 ESMO GI Congress. The trial included 20 patients with microsatellite stable (MSS) and microsatellite instability-high (MSI-H) tumors. After treatment, 78% of MSS patients in the NEST-2 cohort showed at least 50% tumor regression, and 56% achieved complete pathologic responses. The study highlighted manageable side effects and no delays in surgeries due to adverse events. The data suggests BOT/BAL therapy could significantly impact neoadjuvant colon cancer treatment, reducing disease recurrence and minimizing invasive procedures.

Positive

• 78% of MSS patients in the NEST-2 cohort achieved at least 50% tumor regression.
• 56% of MSS patients in the NEST-2 cohort reached complete pathologic responses.
• No surgeries were delayed due to adverse events.
• No new safety concerns emerged during the trial.

Negative

• None.

Oncology Doctor

The results presented at the ESMO GI Conference regarding botensilimab and balstilimab (BOT/BAL) in neoadjuvant colon cancer treatment are nothing short of revolutionary. The data shows a profound efficacy of the BOT/BAL combination, especially in patients with microsatellite stable (MSS) colorectal cancer, which is typically resistant to immunotherapy. The high rates of pathologic response, particularly the complete response rates of 56% in the NEST-2 cohort, are remarkable. These results suggest that the BOT/BAL regimen could potentially redefine the neoadjuvant treatment landscape for MSS colon cancer, offering a new therapeutic avenue that leverages the body's own immune system to achieve tumor reduction without leading to significant adverse events. This could not only improve surgical outcomes but also reduce the need for more invasive treatments in the future.

Investors should note that if these results are consistently replicated in larger studies, Agenus could see substantial growth in its market share and valuation due to the transformative impact of this therapy on colorectal cancer treatment.

Financial Analyst

From a financial perspective, the promising results of the BOT/BAL combination therapy are highly significant for Agenus. The data highlights an effective response in a difficult-to-treat subset of colon cancer patients, which could potentially broaden the company's portfolio and increase its competitive edge in the oncology market. Furthermore, if subsequent trials confirm these findings, Agenus could receive expedited approval from regulatory bodies, leading to accelerated revenue streams. However, investors should remain cautious and watch for additional clinical trial results and regulatory updates before making any investment decisions. The financial implications could be immense, but they hinge on the continued success and acceptance of this therapy in broader clinical settings.

Key points to monitor include regulatory milestones, further clinical trial data and the company's ability to scale production and distribution of these therapies.

Extended BOT/BAL Therapy Yields Pronounced Improvements in Tumor Reductions

LEXINGTON, Mass.--(BUSINESS WIRE)-- Agenus Inc. (“Agenus”) (Nasdaq: AGEN), a leader in developing novel immunological agents to treat various cancers, today announced results from an investigator-sponsored trial (IST) of botensilimab and balstilimab (BOT/BAL) in the neoadjuvant setting for colon cancer. Data were presented at the 2024 European Society for Medical Oncology (ESMO) Gastrointestinal Cancers Congress in Munich, Germany.

Dr. Pashtoon Kasi, the originator of this groundbreaking study, stated, “The rapid and complete resolution of aggressive MSS colorectal cancer tumors observed in this study is unprecedented in the field. The exceptional activity of the BOT/BAL combination therapy in the neoadjuvant setting offers new hope for patients facing this challenging cancer subtype. Furthermore, the pattern of response and the lack of clinical recurrence speaks to the curative potential of one’s own body to fight cancer.”

Study Highlights:

• Enrollment: 20 patients were evaluable at the data cutoff with available pathology results, 17 microsatellite stable (MSS) and 3 high microsatellite instability (MSI-H).
• Treatment Regimens: Both cohorts received one dose of botensilimab with balstilimab. The NEST-1 cohort received one additional dose of balstilimab two weeks later, whereas the NEST-2 cohort received up to 3 additional doses of balstilimab.

Clinical Findings:

• Pathologic Response: In the NEST-2 cohort, 78% (7/9) of MSS patients achieved pathologic responses of at least 50% tumor regression, with 56% (5/9) reaching complete pathologic responses.
• Surgical Outcomes and Safety: No surgeries were delayed due to adverse events, and no patients had unresolved immune related adverse events. Side effects were manageable, and no new safety concerns emerged.

	Pathologic Response (>50% Regression)	Complete Pathologic Response (100% Regression)
NEST-1 (N=10)
MSS (N=8)	5 (63%)	1 (13%)
MSI-H (N=2)	2 (100%)	1 (50%)
NEST-2 (N=10)
MSS (N=9)	7 (78%)	5 (56%)
MSI-H (N=1)	1 (100%)	1 (100%)
Overall
MSS (N=17)	12 (71 %)	6 (35%)
MSI-H (N=3)	3 (100%)	2 (67%)

“The significant tumor reductions observed with the early use of BOT/BAL therapy before surgery underscore its paradigm-changing potential in neoadjuvant colon cancer, potentially minimizing the rate of disease recurrence and the need for invasive procedures and chemotherapy in the future,” said Dr. Steven O’Day Chief Medical Officer at Agenus. “The responses in MSS patients were particularly profound, and extending the treatment duration in the NEST-2 cohort further amplified these effects. We are focused on expanding BOT/BAL’s application in the neoadjuvant setting to improve treatment for individuals living with cancer.”

The presentation is available on the Agenus website at https://agenusbio.com/publications.

About Botensilimab

Botensilimab is a human Fc enhanced CTLA-4 blocking antibody designed to boost both innate and adaptive anti-tumor immune responses. Its novel design leverages mechanisms of action to extend immunotherapy benefits to "cold" tumors which generally respond poorly to standard of care or are refractory to conventional PD-1/CTLA-4 therapies and investigational therapies. Botensilimab augments immune responses across a wide range of tumor types by priming and activating T cells, downregulating intratumoral regulatory T cells, activating myeloid cells and inducing long-term memory responses.

Approximately 900 patients have been treated with botensilimab in phase 1 and phase 2 clinical trials. Botensilimab alone, or in combination with Agenus’ investigational PD-1 antibody, balstilimab, has shown clinical responses across nine metastatic, late-line cancers. For more information about botensilimab trials, visit www.clinicaltrials.gov with the identifiers NCT03860272, NCT05608044, NCT05630183, and NCT05529316.

About Colorectal Cancer

Colorectal cancer (CRC) is the second leading cause of cancer death in the United States, comprising an estimated 8.3% of cancer-related deaths annually. Although overall mortality from CRC has declined, survival remains poor for advanced disease, and the burden is shifting to a younger population. Alarmingly, from 1995 to 2019, the number of patients under the age of 55 who were diagnosed with CRC in the United States nearly doubled.

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 @agenus_bio. Information that may be important to investors will be routinely posted on our website and social media channels.

Forward-Looking Statements

This press release contains forward-looking statements that are made pursuant to the safe harbor provisions of the federal securities laws, including statements regarding a its botensilimab and balstilimab programs, expected regulatory timelines and filings, and any other statements containing the words "may," "believes," "expects," "anticipates," "hopes," "intends," "plans," "forecasts," "estimates," "will," “establish,” “potential,” “superiority,” “best in class,” and similar expressions are intended to identify forward-looking statements. These forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially. These risks and uncertainties include, among others, the factors described under the Risk Factors section of our most recent Annual Report on Form 10-K for 2023, and subsequent Quarterly Reports on Form 10-Q filed with the Securities and Exchange Commission. Agenus cautions investors not to place considerable reliance on the forward-looking statements contained in this release. These statements speak only 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.

View source version on businesswire.com: https://www.businesswire.com/news/home/20240628177376/en/

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Source: Agenus Inc.

FAQ

What were the results of the BOT/BAL trial for colon cancer presented at ESMO GI Conference 2024?

The trial showed that 78% of MSS patients in the NEST-2 cohort achieved at least 50% tumor regression, and 56% reached complete pathologic responses.

How effective was the BOT/BAL therapy in MSS colon cancer patients?

In the NEST-2 cohort, 78% of MSS patients achieved at least 50% tumor regression, with 56% reaching complete pathologic responses.

Were there any safety concerns in the BOT/BAL trial for colon cancer?

No new safety concerns emerged, and side effects were manageable. No surgeries were delayed due to adverse events.

What is the significance of the BOT/BAL trial results for colon cancer?

The trial results suggest that BOT/BAL therapy could significantly reduce disease recurrence and minimize the need for invasive procedures in neoadjuvant colon cancer treatment.

What percentage of MSS patients showed complete tumor regression in the NEST-2 cohort of the BOT/BAL trial?

56% of MSS patients in the NEST-2 cohort showed complete tumor regression.