U.S. BLA Filing in Microsatellite Stable (MSS) Metastatic Colorectal Cancer (CRC) Planned for Midyear 2024

Potential Accelerated Filings for Advanced Pancreatic Cancer and Melanoma in 2025

Opportunity to Expand into Early-Stage Cancers Supported by Compelling Neoadjuvant CRC Data

Live Webcast Today at 1:00 p.m. EDT

Agenus Inc. (Nasdaq: AGEN), a leader in developing novel immunological agents to treat cancers, today announced first-time and updated data from its ongoing botensilimab/balstilimab (BOT/BAL) clinical programs in advanced colorectal cancer (CRC), neoadjuvant CRC, pancreatic cancer, non-small cell lung cancer (NSCLC), melanoma, and sarcoma. Members of the Agenus leadership team along with key opinion leaders will discuss these findings during a live webcast at 1:00 p.m. EDT (19:00 CEST) at a corporate event at the European Society for Medical Oncology 2023 Conference.

“These new and updated data underscore BOT’s broad effectiveness across several advanced solid tumors, demonstrating its potential beyond first-generation immunotherapies and current treatments,” said Dr. Steven O’Day, Chief Medical Officer. “BOT’s versatility, alone, in combination with BAL, or in combination with other standard of care therapies, in early and late-stage solid tumors, positions Agenus to transform cancer care, offering immense promise to patients.”

Key highlights across solid tumors include:

Extended Follow-up and Additional Data in Refractory MSS CRC Demonstrate Improved Responses and Durability

In 70 efficacy evaluable patients with MSS CRC and no active liver metastases:

• Confirmed (RECIST 1.1) overall response rate (ORR) of 24% was observed, compared to 2.8% reported with standard of care (SOC) in 2/3L+ MSS CRC patients with no active liver metastases¹.
• 12-month overall survival (OS) of 74% and median OS (mOS) not yet reached. Median follow up now 12.3 months.

Subsequent data from expanded cohorts and early signals from a 230 patient Phase 2 trial is consistent with the earlier cohort of 70 patients. Based on the totality of the evidence from the Phase 1 and Phase 2 trials, Agenus plans to submit its Biologics License Application (BLA) to the U.S. Food & Drug Administration (FDA) for BOT/BAL in patients with 2/3L+ MSS CRC in midyear 2024. Interactions with U.S. and EU regulatory agencies are ongoing.

Robust Clinical Outcomes in Neoadjuvant MSS CRC Underscore BOT/BAL’s Potential in Earlier-Stage Patients*

• All patients treated with one dose of BOT and two doses of BAL.
• After dosing, observations of responses were made within approximately four-weeks prior to surgery.
• 100% (3/3) of patients with MSI-H CRC had major pathological responses (>90%).
• 67% (6/9) patients with MSS CRC had pathological responses of >50%, which includes two complete pathological responses.
• These findings offer an alternative path to minimize or eliminate radical rectal surgery and its associated morbidities such as colostomy dependance and sexual dysfunction, and potentially avoid the need for systemic chemotherapy.
• Agenus plans to prioritize neoadjuvant development and is evaluating study design for further regulatory activity.

Compelling Activity from Dose-escalation Portion of Phase 2 BOT/Chemotherapy Combination in Advanced (2L) Pancreatic Cancer

• In FOLFIRINOX relapsed/refractory (2L) pancreatic cancer, 80% of evaluable patients (n=5; 150mg BOT+gem-Abraxane) experienced sustained tumor marker reductions. All patients had liver metastases.
• Two partial responses were at 16 weeks with target lesion reduction of -47% (confirmed) and -37% (pending confirmation), and both responses remain ongoing.
• Two other patients showed stable disease with tumor reduction of -20% and -13% at 8 weeks and remain on study awaiting 16-week scans.
• A Phase 2 randomized study is enrolling.

Monotherapy Activity in CTLA-4 Relapsed/Refractory Advanced (2L+) Melanoma

• Phase 1 expansion cohort in relapsed/refractory (2L+) melanoma (n=10) showed a 30% ORR and 60% disease control rate; 8/10 patients had multiple prior lines including anti-PD-1/CTLA-4 and failed BRAF targeted therapy (n=5).
• An accelerated Phase 2 trial in patients who have failed anti-CTLA-4 and PD-1 is underway; BOT monotherapy cohort is fully enrolled and BOT/BAL combination is enrolling.

Compelling Responses in Refractory NSCLC

• Patients treated with PD(L)-1 refractory NSCLC were treated with BOT/BAL combination and showed a 56% ORR and 89% disease control rate (n=9).
• Importantly, in patients with EGFR mutations refractory to SOC responded to the BOT/BAL combo, with one patient experiencing an -90% tumor reduction** at 12 weeks and the second having a -42% tumor reduction at 6 weeks and is pending confirmation.
• Expansion cohorts are underway with anticipated enrollment of 100 patients by 1Q 2024.
• Additional data from this study will be reported in midyear 2024.

Broad and Durable Activity in Advanced Sarcomas

Updated data was presented at ESMO 2023 from the Phase 1b study in 41 efficacy evaluable heavily pretreated advanced sarcoma patients, demonstrating durability with extended follow-up and additional activity in difficult-to-treat subtypes such as leiomyosarcoma.

• BOT/BAL combination demonstrated 6-month progression-free survival of 40%, ORR of 20%, and median response duration of 19.4 months (iRECIST).
• Differential responses observed by dose level, with 29% ORR at 2 mg/kg BOT compared to 15% at 1 mg/kg BOT.

Webcast Details

A live webcast will be held today at 19:00 – 21:00 CEST (1:00 p.m. – 3:00 p.m. EDT). To register for the webcast, please click here.

References:

1. 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

*Investigator Sponsored Trial

**Investigator reported, subject to change.

About Botensilimab

Botensilimab is an investigational multifunctional anti-CTLA-4 immune activator (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 750 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 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 2022, 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.

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