AGEN2373 / Agenus, Gilead - LARVOL DELTA

Comparing Neoadjuvant/Adjuvant GVAX vs a mKRASvax Given With Anti-PD-1 and Anti-CD137 for Surgically Resectable Pancreatic Cancer (clinicaltrials.gov) - P1/2 | N=38 | Not yet recruiting | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

IO biomarker • New P1/2 trial • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • CD20

C-1100-01: Anti-CD137 and Anti-CTLA-4 Monoclonal Antibody in Patients With Advanced Cancer (clinicaltrials.gov) - P1 | N=91 | Completed | Sponsor: Agenus Inc. | Active, not recruiting ➔ Completed | N=67 ➔ 91 | Trial completion date: Jun 2027 ➔ Nov 2024 | Trial primary completion date: Jun 2025 ➔ Feb 2024

Enrollment change • Monotherapy • Trial completion • Trial completion date • Trial primary completion date • Melanoma • Oncology • BRAF • PD-L1

Ligand Reports First Quarter 2024 Financial Results (Businesswire) - "On May 7, Ligand announced a $100 million royalty financing agreement with Agenus, Inc. Under the terms of the agreement, in exchange for an initial $75 million payment, Ligand will receive 18.75% of the royalties and 31.875% of the future milestones on six Agenus-partnered oncology programs including BMS-986442 (Bristol Myers Squibb), AGEN2373 (Gilead Sciences), INCAGN2385 and INCAGN2390 (Incyte), MK-4830 (Merck), and UGN-301 (UroGen Pharma)."

Financing • Licensing / partnership • Oncology

Anti-CD137 and Anti-CTLA-4 Monoclonal Antibody in Patients With Advanced Cancer (clinicaltrials.gov) - P1 | N=67 | Active, not recruiting | Sponsor: Agenus Inc. | Recruiting ➔ Active, not recruiting | N=200 ➔ 67

Combination therapy • Enrollment change • Enrollment closed • Metastases • Monotherapy • Melanoma • Oncology • BRAF • PD-L1

A phase 1 study of AGEN2373, a novel CD137 agonist antibody designed to avoid hepatoxicity, in patients with advanced solid tumors. (ASCO 2023) - P1 | "Notable responses include: a pt with vulvar SCC who had progressed rapidly on pembrolizumab and had a confirmed partial response (cPR) while remaining on AGEN2373 x 2 mg/kg q2w for ~40 wks, and a pt with ampullary carcinoma with 4 prior regimens had a cPR on AGEN2373 x 6 mg/kg q3w with complete resolution of the pancreatic lesion. AGEN2373 showed objective responses as monotherapy in heavily pretreated pts with solid tumors and was well-tolerated with no evidence of hepatotoxicity. This distinguishes AGEN2373 from previous CD137-targeted agents that reported dose-limiting hepatotoxicity. Combination therapy with botensilimab, a novel Fc-enhanced CTLA-4 antagonist, is being studied in pts with PD(L)-1 pretreated melanoma."

Clinical • IO biomarker • Metastases • P1 data • Ampulla of Vater Carcinoma • Colorectal Cancer • Fatigue • Gastrointestinal Cancer • Hepatology • Immune Modulation • Melanoma • Oncology • Prostate Cancer • Sarcoma • Solid Tumor • TNFA

Agenus Presents Positive Efficacy and Safety Outcomes for AGEN2373 at ASCO (Businesswire) - "'AGEN2373 has shown meaningful single agent activity and a favorable safety profile without evidence of liver toxicity in patients with heavily pretreated cold and immunotherapy resistant tumors,' said Dr. Steven O'Day, MD...'AGEN2373 is designed to selectively boost tumor immunity while limiting hepatotoxicity and off-target effects associated with systemic CD137 activation. These encouraging monotherapy results support further clinical trials for AGEN2373 alone and in combination with our novel immunotherapy programs.'"

Media quote

Agenus Presents Positive Efficacy and Safety Outcomes for AGEN2373 at ASCO (Businesswire) - P1 | N=200 | NCT04121676 | Sponsor: Agenus Inc | "Agenus...presented complete results from the monotherapy arm of the first-in-human dose escalation study of AGEN2373 (CD137 agonist) at the American Society of Clinical Oncology (ASCO) Annual Meeting. AGEN2373 demonstrated objective responses, clinical benefit, and was well tolerated in heavily pre-treated patients with solid tumors....Notable responses in the dose escalation study include: Confirmed partial response in a patient with vulvar squamous cell carcinoma who progressed on prior pembrolizumab. Confirmed partial response with complete resolution of the pancreatic lesion in a patient with ampullary carcinoma. Confirmed 38% reduction in target liver lesions in a castrate-resistant prostate cancer that was non-evaluable by RECIST due to palliative radiation for bone metastases."

P1 data • Oncology • Solid Tumor

Agenus Provides Corporate Update and First Quarter 2023 Financial Results (Businesswire) - "Upcoming Presentations...Data from a single-arm, open-label Phase 2 study of balstilimab and zalifrelimab (1st generation CTLA-4) plus doxorubicin in patients with advanced sarcomas selected for oral presentation at the ASCO 2023 Annual Meeting, to be held June 2-6 in Chicago, IL; Complete results from the monotherapy arm of the first-in-human dose escalation study of AGEN2373 in patients with advanced solid tumors will also be presented in a poster discussion at ASCO."

P1 data • P2 data • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Agenus to Present at the American Society of Clinical Oncology 2023 Annual Meeting (Businesswire) - "Agenus...announced plans to present clinical data at the American Society of Clinical Oncology (ASCO) 2023 Annual Meeting....Data from a single-arm, open-label Phase 2 study of balstilimab (PD-1 antagonist) and zalifrelimab (first generation CTLA-4 antagonist) plus doxorubicin in patients with advanced sarcomas will be presented at an oral session on Monday, June 5 from 11:30am - 2:30pm CDT. Complete results from the monotherapy arm of the first-in-human dose escalation study of AGEN2373 (CD137 agonist) in patients with advanced solid tumors will be presented at a poster discussion on Saturday, June 3rd from 3:00pm - 4:30pm CDT."

P1 data • P2 data • Oncology • Sarcoma • Solid Tumor

Anti-CD137 Monoclonal Antibody in Patients With Advanced Cancer (clinicaltrials.gov) - P1; N=86; Recruiting; Sponsor: Agenus Inc.; N=42 ➔ 86; Trial completion date: Dec 2023 ➔ Dec 2024; Trial primary completion date: Sep 2022 ➔ Sep 2023

Clinical • Combination therapy • Enrollment change • Monotherapy • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

Anti-CD137 and Anti-CTLA-4 Monoclonal Antibody in Patient With Advanced Cancer (clinicaltrials.gov) - P1; N=200; Recruiting; Sponsor: Agenus Inc.; N=86 ➔ 200; Trial completion date: Dec 2024 ➔ Jun 2027; Trial primary completion date: Sep 2023 ➔ Jun 2025

Clinical • Combination therapy • Enrollment change • Monotherapy • Trial completion date • Trial primary completion date • Melanoma • Oncology • Solid Tumor • BRAF • PD-L1

Agenus Reports Fourth Quarter and Full Year 2022 Financial Results and Outlines 2023 Objectives (GlobeNewswire) - "Additional 2023 Catalysts and Operational Objectives: Complete enrollment of the Phase 1b study of AGEN2373 (anti-CD137) and botensilimab in melanoma. Initiate combination cohorts of AGEN1571 (anti-ILT2) with botensilimab and balstilimab....Advance 7 existing clinical collaborations evaluating combinations of external agents with our PD-1 and CTLA-4 antibodies sponsored and executed by partners."

Licensing / partnership • Trial status • Oncology • Solid Tumor

Botensilimab modulates innate and adaptive gene expression programs resulting in superior immune stimulation relative to a first-generation anti-CTLA-4 antibody (SITC 2022) - "In patients with advanced solid tumors, botensilimab alone and in combination with balstilimab (anti-programmed cell death protein 1 [PD-1] antibody) demonstrated durable clinical responses in nine different immunotherapy-resistant or poorly immunogenic tumor types. Increased expression of LILRB1 and TNFRSF9 in botensilimab-treated immune subsets supports the combination strategies with AGEN1571 (anti-ILT2) and AGEN2373 (anti-CD137) currently under clinical investigation. Ethics Approval This study was approved by WCG IRB Ethics Board; approval number 120160614."

IO biomarker • Oncology • Solid Tumor • CD4 • CD8 • GZMB • LILRB1 • TNFA

Agenus Provides Corporate Update and Second Quarter 2022 Financial Report (GlobeNewswire) - "Clinical-stage pipeline continues to advance: Company to present additional Phase 1b botensilimab expansion cohort data with longer follow-up at a major medical conference later this year; Dosing underway in Phase 1 study to evaluate AGEN1571 as a monotherapy and in combination with botensilimab and/or balstilimab in participants with advanced solid tumors; Enrollment continues in Agenus directed trials, such as a combination study involving AGEN2373 (CD137 agonist) and botensilimab."

P1 data • Trial status • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

"$AGEN Agenus’ CD137 Agonist (AGEN2373) Advances in the Clinic, Triggering Milestone Payment from Gilead https://t.co/oma7Owd6TY" (@stock_titan)

Agenus’ CD137 Agonist (AGEN2373) Advances in the Clinic, Triggering Milestone Payment from Gilead (GlobeNewswire) - "Agenus...announced receipt of a $5M clinical milestone payment for AGEN2373 (conditionally active CD137 agonist)....Gilead currently has an exclusive option to license AGEN2373. Agenus retains the right to opt-in to share Gilead’s development and commercialization costs in the United States in exchange for a 50:50 profit share and US co-commercialization rights."

Commercial • Financing • Melanoma • Oncology • Skin Cancer • Solid Tumor

Clinical Activity of AGEN1181 Demonstrated Across Nine Treatment-Resistant Cancers at SITC (GlobeNewswire) - "Phase 2/3 trials to be initiated in colorectal and gynecological cancers: Based on these data, multi-arm, randomized phase 2/3 trials investigating AGEN1181 as monotherapy and in combination with balstilimab in MSS-CRC and gynecological cancers (ovarian and MSS-endometrial cancer) are being initiated. The design of these trials may support a potential filing for full and/or accelerated approval based on the magnitude of benefit demonstrated in the studies. Combination studies of AGEN1181 with AGEN2373, a conditionally active CD137 agonist, are expected to begin later this year in PD-1 refractory melanoma."

New P2/3 trial • New trial • Cervical Cancer • Endometrial Cancer • Gynecologic Cancers • Melanoma • Oncology

[VIRTUAL] Initial findings of the first-in-human phase I study of AGEN2373, a conditionally active CD137 agonist antibody, in patients (pts) with advanced solid tumors. (ASCO 2021) - P1 | "AGEN2373 demonstrates good tolerability in pts with advanced solid tumors, with a safety profile characterized by a lack of hepatotoxicity frequently observed with CD137-targeting antibodies . These findings underscore the suitability of AGEN2373 as a potential partnering agent for other immunomodulatory agents, including planned expansion as combination therapy with balstilimab (anti-PD-1)."

Clinical • P1 data • Fatigue • Hepatology • Immune Modulation • Inflammation • Leiomyosarcoma • Oncology • Sarcoma • Solid Tumor • TNFA

Agenus’ Presentations at ASCO 2021 Demonstrate Differentiated Activity of Balstilimab and Provide Clinical Update on AGEN2373 (GlobeNewswire) - P1, N=86; NCT04121676; Sponsor: Agenus Inc; "In this first-in-human study of AGEN2373 in patients with advanced solid tumors, no dose limiting toxicities were seen at doses up to 3 mg/kg; notably, no liver toxicity has been observed well above the threshold at which liver toxicity is usually seen with other CD-137 agonist antibodies. Five patients demonstrated stable disease out of 22 patients treated with AGEN2373 monotherapy, with prolonged stable disease observed in three of these patients."

P1 data • Oncology • Solid Tumor

Agenus to Present at the 2021 ASCO Annual Meeting (GlobeNewswire) - “Agenus…announced that it will give two presentations at the 2021 American Society for Clinical Oncology (ASCO) Annual Meeting poster sessions. The ASCO meeting will be held from June 4 – 8, 2021. Presentation Details: Abstract title: Differentiated activity profile for the PD-1 inhibitor balstilimab; Abstract title: Initial findings of the first-in-human Phase I study of AGEN2373, a conditionally active CD137 agonist antibody, in patients (pts) with advanced solid tumors.”

Clinical data • P1 data • Gynecologic Cancers • Oncology • Solid Tumor

Agenus Presents New Data on Balstilimab and AGEN2373 in ASCO Abstracts (GlobeNewswire) - P1, N=86; NCT04121676; Sponsor: Agenus Inc.; "In this first-in-human study of AGEN2373 in patients with advanced solid tumors, no dose limiting toxicities were seen at doses up to 3 mg/kg; notably, no liver toxicity has been observed. Five patients demonstrated stable disease out of 19 patients treated with AGEN2373 monotherapy, including one heavily pretreated patient with metastatic leiomyosarcoma who had progressed on prior combination checkpoint immunotherapy."

P1 data • Leiomyosarcoma • Oncology • Sarcoma • Solid Tumor

[VIRTUAL] AGEN2373 is a CD137 agonist antibody designed to leverage optimal CD137 and FcγR co-targeting to promote antitumor immunologic effects (SITC 2020) - No abstract available

Oncology

[VIRTUAL] AGEN2373 is a CD137 agonist antibody designed to leverage optimal CD137 and FcγR co-targeting to promote antitumor immunologic effects (SITC 2020) - No abstract available

Oncology

"Meet our #SITC2020 presenters! Dr. Claire Galand @ClaireGaland is the senior scientist for the #pharmacology team at $AGEN. She currently leads the preclinical research for AGEN2373, our anti-CD137 #Immunotherapy #oncology" (@Agenus_Bio)

Preclinical • Oncology

Agenus Presents Additional Clinical Responses and Novel Biomarker Data at SITC2020 (GlobeNewswire) - P1, N=42; NCT04121676; Sponsor: Agenus Inc; "SD in 4 patients with durable disease stabilization in an ovarian cancer patient; No liver toxicity in patients dosed up to 1mg/kg; AGEN2373 clinical data indicate increased trafficking of CD8 and CD4 T cells, and mature NK cells in the tumor microenvironment; 2373 also promotes robust depletion of intratumoral Tregs"

P1 data • Oncology • Solid Tumor