ESMO 2023: Agenus’ Botensilimab/Balstilimab Combination Delivers Durable Responses across Multiple Sarcoma Subtypes

Agenus Inc. (Nasdaq:AGEN), a leader in developing novel immunological agents to treat various cancers, today announced expanded data from the company’s phase 1b study of botensilimab (BOT, multifunctional immune activator) in combination with balstilimab (BAL, anti-PD-1) in patients with advanced sarcomas. The results were presented in an oral presentation at the European Society for Medical Oncology (ESMO) Congress 2023.

Relapsed/refractory sarcoma represents a significant unmet medical need where existing standard of care options and previous immunotherapies have shown limited activity. At present, available treatments for advanced soft tissue sarcoma patients only have modest activity. The sarcoma cohort presented is part of a larger phase 1b study evaluating the safety, efficacy, and dose optimization of BOT alone and in combination with BAL in multiple advanced solid tumors.

"These results reinforce the promising potential of BOT+BAL in multiple cold, treatment-resistant solid tumors," said Dr. Steven O’Day, Chief Medical Officer. "Notably, we observed several durable responses extending past one year, including patients with visceral angiosarcoma, which is traditionally unresponsive to immunotherapy, as well as other cold subtypes like leiomyosarcoma. As we expand the study, we aim to focus on key subsets and dosing strategies to maximize benefit for patients.”

“As the study has advanced, BOT+BAL continues to demonstrate encouraging results in a larger population of patients with difficult to treat sarcomas, with a median response duration of 19.4 months and a 40% 6-month progression-free survival rate. We're also seeing a dose-dependent effect, with a 29% objective response rate at 2 mg/kg,” said Dr. Breelyn Wilky, MD, Director of Sarcoma Medical Oncology at the University of Colorado, and study investigator.

Study Design and Highlights

A total of 41 evaluable patients received either 1 or 2 mg/kg BOT every 6 weeks and 3 mg/kg BAL every 2 weeks.

Patient Demographics

• Majority of patients had either angiosarcoma (29%) or leiomyosarcoma (39%) subtypes
• Patients were heavily pre-treated, with a median of three prior lines of therapy, including 16% who received prior PD-(L)1 therapy
• Majority of patients had biomarkers associated with poor response to immunotherapy:
  • 87% had a low tumor mutation burden (<10 mutations per megabase)
  • 74% of patients were PD-L1 negative by immunohistochemistry

Clinical Findings

Efficacy in all comers (as measured by iRECIST; n=41)

• 40% 6-month PFS
• 20% ORR
  • 29% ORR at the BOT 2 mg/kg dose level
  • 15% ORR at the 1 mg/kg dose level
• 63% disease control rate (best response of a complete response + partial response + stable disease)
• Median duration of response was 19.4 months

Safety in all comers (N=50)

• No new safety signals reported, with tolerability consistent across tumor types
• Adverse events were generally manageable and reversible
• Diarrhea/colitis was the most clinically significant immune-mediated adverse event
• No grade 4 or 5 treatment-related adverse events and no related cases of irreversible events such as hypophysitis, pneumonitis, hepatitis, or myocarditis were reported

Presentation Details

Abstract Title: Efficacy and safety of botensilimab (BOT) plus balstilimab (BAL) in patients (pts) with refractory metastatic sarcoma (NCT03860272)

Abstract Number: 1919MO

Presenting Author: Breelyn A. Wilky, MD, Director of Sarcoma Medical Oncology, Deputy Associate Director for Clinical Research, University of Colorado Cancer Center

Session Date and Time: 10/21/2023, 10:15 a.m. – 11:45 a.m. CEST

Presentation Date and Time: 10/21/2023, 11:00 a.m. – 11:05 a.m. CEST

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

References

1 . D’Angelo SP, et al. Lancet Oncol. 2018;19

2. Chen JL, et al. J Clin Oncol. 2020;38(15)_suppl:11511-11511

3. Wagner MJ, et al. J Immunother Cancer. 2021;9:e002990.

About Botensilimab

Botensilimab is an investigational multifunctional anti-CTLA-4 immune activator 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 other 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 600 patients have been treated with botensilimab in phase 1 and phase 2 clinical trials. Botensilimab alone, or in combination with Agenus’ investigational anti-PD-1, 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 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 Agenus’s corporate event at ESMO and related presentation about its botensilimab programs 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 Quarterly Report on Form 10-Q or Annual Report on Form 10-K 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.

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