• Overall response rates ranged from 22% in microsatellite stable colorectal cancer (MSS-CRC) to 60% in PD-(L)1 refractory non-small cell lung cancer (NSCLC)
  
• Initiated Phase 2 ACTIVATE trials of botensilimab in advanced MSS-CRC and advanced melanoma; pancreatic cancer to follow before year-end
  

LEXINGTON, Mass., Nov. 14, 2022 (GLOBE NEWSWIRE) -- Agenus (Nasdaq: AGEN), an immuno-oncology company with a broad pipeline targeting cancer and infectious disease, announced expanded data from the Company’s Phase 1 study of botensilimab (Fc-enhanced anti-CTLA-4) and balstilimab (anti-PD-1) in patients with treatment-resistant tumors, including MSS-CRC, ovarian, sarcoma and NSCLC. The data presented represents four of the most mature data sets from the nine cancer types where responses have been observed to date. The data was presented at a plenary session at the Society for Immunotherapy of Cancer (SITC) annual meeting and a company-hosted R&D event.

“This expanded dataset demonstrates the tremendous potential of botensilimab and balstilimab to treat a wide range of immunotherapy-resistant tumors,” said Steven O’Day, M.D., Chief Medical Officer of Agenus. “Importantly, the superior efficacy we observed in our MSS-CRC presentation at GI ESMO earlier this year has remained consistent across a larger dataset. Further, we are seeing a strong signal with higher response rates than has been reported with other immunotherapies in multiple tumor types, including anti-PD-(L)1 relapsed/refractory NSCLC. These data provide compelling support for our ongoing Phase 2 botensilimab development program and highlight the broad therapeutic potential of botensilimab across solid tumors.”

Study Design and Highlights

Out of over 250 enrolled patients, data on 125 patients has matured to efficacy and safety evaluation. These include four primary expansion cohorts in MSS CRC, recurrent platinum refractory/resistant ovarian, sarcoma and PD-(L)1 relapsed/refractory NSCLC. Patients in these cohorts received either 1 or 2 mg/kg botensilimab every 6 weeks and 3 mg/kg balstilimab every 2 weeks, with imaging assessments every six weeks. Fixed dosing was also permitted whereby patients received botensilimab 150 mg every 6 weeks, and balstilimab 450 mg every 3 weeks. Trial enrollees were heavily pre-treated with the majority receiving at least 3 prior lines of therapy.

MSS-CRC:

• 59 evaluable patients
  • 76% failed on ≥3 prior lines of therapy
  • 34% did not respond to prior experimental I-O
• 22% overall response rate: 1 complete response (CR), 12 partial responses (PR)
  • Other PD-(L)1 + CTLA-4 combination regimens in comparable patient populations achieved only 1-5% response rates^1,2
• 73% disease control rate
• Median duration of response not reached
  • 69% of responses are ongoing
  • 31% of responses have already exceeded 1 year
• Median Progression Free Survival (mPFS) of 4.1 months; 12 month Overall Survival (OS) of 60.4%; median Overall Survival (mOS) has not been reached
  • Other PD-(L)1 + CTLA-4 combination regimens in comparable patient populations achieved a 1.8 mPFS and 6.6 mOS
    

Ovarian:

• 19 evaluable patients
  • 71% received ≥3 prior lines of therapy
• 26% overall response rate: 1 CR, 4 PRs
  • Other PD-(L)1 + CTLA-4 combination regimens in comparable patient populations achieved only 3-10% response rates^3,4
• 63% disease control rate
• Median duration of response not reached

Sarcoma:

• 12 evaluable patients
  • 73% received ≥3 prior lines of therapy
• 42% overall response rate: 1 CR, 4 PRs
  • Other PD-(L)1 + CTLA-4 combination regimens in comparable patient populations achieved only 12-16% response rates^5,6
• 50% response rate in angiosarcoma, including 3 of 4 patients with visceral angiosarcoma
  • Other PD-(L)1 + CTLA-4 combinations achieved only 20-25% response rates with no reported responses in 7 treated patients with visceral angiosarcoma^6,7
• 67% disease control rate
• Median duration of response not reached
  • 60% of responses have already exceeded 1 year and are ongoing
    

Anti-PD-(L)1 Relapsed/Refractory NSCLC:

• 5 evaluable patients (including 1 evaluable patient dosed after the data cut-off)
• 60% overall response rate
  • Other PD-(L)1 + CTLA-4 combination regimens in comparable patient populations achieved only 6-13% response rates^8,9
• 80% disease control rate
• Median duration of response not reached
  • 67% of responses are ongoing

Tolerability:

Botensilimab was well tolerated, with no new immune-mediated safety signals outside of those observed in the class. Rates of gastrointestinal and skin toxicities were comparable to those reported with first-generation CTLA-4 inhibitors, while other immune mediated toxicities were less frequent than expected, consistent with botensilimab’s design to reduce complement binding.

“There is an urgent need to develop new therapies for patients suffering with cold and refractory tumors as current standards of care typically offer only single-digit response rates, “said Breelyn Wilky, M.D., Principal Investigator and Director of Sarcoma Medical Oncology at the University of Colorado School of Medicine. “The robust and durable clinical responses demonstrated by botensilimab and balstilimab in this study across a wide spectrum of refractory tumor types, coupled with its well-tolerated safety profile, provide strong support for the further development of this combination in a broad range of patients.”

Presentation Details:

Abstract Number: 778

Abstract Title: Botensilimab, a novel innate/adaptive immune activator, plus or minus balstilimab (anti-PD-1) in 'cold' and I-O refractory metastatic solid tumors

Presenting Author: Breelyn A. Wilky, M.D., Director of Sarcoma Medical Oncology, Deputy Associate Director for Clinical Research University of Colorado School of Medicine

The data were presented on Saturday, November 12 at both the Society for Immunotherapy of Cancer and “The Road Taken” R&D event hosted offsite by Agenus. An archived version of each presentation will be available on the Agenus website.

References
1 Chen et al. JAMA Oncol. 2020
2 Overman et al. ASCO 2016
3 https://clinicaltrials.gov/ct2/show/results/NCT01928394
4 Hinchcliff et al. Gynecologic Oncology 2021
5 D’Angelo et al. Lancet Oncology 2018
6 Somaiah et al. Lancet Oncology 2022
7 Wagner et al JITC 2021
8 https://clinicaltrials.gov/ct2/show/results/NCT02750514
9 Fisher et al. ASCO 2019

About Agenus

Agenus is a clinical-stage immuno-oncology company focused on the discovery and development of therapies that engage the body's immune system to fight cancer and infections. The Company's vision is to expand the patient populations benefiting from cancer immunotherapy by pursuing combination approaches that leverage a broad repertoire of antibody therapeutics, adoptive cell therapies (through its subsidiary MiNK Therapeutics), and adjuvants (through its subsidiary SaponiQx). The Company is equipped with a suite of antibody discovery platforms and a state-of-the-art GMP manufacturing facility with the capacity to support clinical programs. Agenus is headquartered in Lexington, MA. For more information, please visit www.agenusbio.com and our Twitter handle @agenus_bio. Information that may be important to investors will be routinely posted on our website and Twitter.

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 relating to our technologies, therapeutic candidates, and capabilities, for instance, statements regarding therapeutic benefit and efficacy, mechanism of action, potency, durability, and safety profile of our therapeutic candidates, both alone and in combination with each other and/or other agents; statements regarding future plans, including research, clinical, regulatory, and commercialization plans; and any other statements containing the words "may," "believes," "expects," "anticipates," "hopes," "intends," "plans," "will" 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 and available on our website: www.agenusbio.com. 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.

Contact

Agenus Inc.
Nico Frelick
Investor Relations
781-674-4616
nico.frelick@agenusbio.com