dalutrafusp alfa (AGEN1423) / Agenus - LARVOL DELTA

A phase 2 study of botensilimab and AGEN1423, an anti-CD73-TGFβ-trap bifunctional antibody, in subjects with advanced pancreatic cancer. (ASCO-GI 2026) - P2 | "Funded by Agenus Inc. Clinical Trial Registration Number: NCT05632328 The full, final text of this abstract will be available on Jan 05 at 05:00 PM EST."

Clinical • Metastases • P2 data • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • TGFB1

A phase 2 study of botensilimab and AGEN1423, an anti-CD73-TGFβ-trap bifunctional antibody, with or without chemotherapy in subjects with advanced pancreatic cancer. (ASCO 2025) - P2 | "In Cohort 2, 12 additional patients with disease progression on first-line fluorouracil-based chemotherapy will be enrolled to receive second-line gemcitabine and nab-paclitaxel in combination with AGEN1423 30mg/kg IV Q2W for 4 doses + BOT 150mg IV Q6W. Translational endpoints include the characterization of the transcriptional signatures in paired biopsies obtained before and on-treatment with BOT + AGEN1423, as well as the changes in cell composition of the TME following treatment using multiplexed immunofluorescence spatial technology. Enrolment has started and accrual is anticipated to complete in Q4 2025."

Clinical • Metastases • P2 data • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CD73 • CTLA4 • TGFB1

AGEN1423 and Botensilimab w/ or w/o Chemo in PDAC (clinicaltrials.gov) - P2 | N=24 | Active, not recruiting | Sponsor: Bruno Bockorny | Recruiting ➔ Active, not recruiting

Enrollment closed • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

Platform Study of Immunotherapy Combinations in Colorectal Cancer Liver Metastases (clinicaltrials.gov) - P2 | N=24 | Recruiting | Sponsor: Weill Medical College of Cornell University | Trial primary completion date: Sep 2025 ➔ Sep 2026

Trial primary completion date • Colorectal Cancer • Hepatology • Oncology • Solid Tumor

AGEN1423 and Botensilimab w/ or w/o Chemo in PDAC (clinicaltrials.gov) - P2 | N=24 | Recruiting | Sponsor: Bruno Bockorny | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Metastases • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

Platform Study of Immunotherapy Combinations in Colorectal Cancer Liver Metastases (clinicaltrials.gov) - P2 | N=24 | Recruiting | Sponsor: Weill Medical College of Cornell University | Not yet recruiting ➔ Recruiting

Enrollment open • Colorectal Cancer • Gastrointestinal Cancer • Hepatology • Oncology • Solid Tumor • CD8

Platform Study of Immunotherapy Combinations in Colorectal Cancer Liver Metastases (clinicaltrials.gov) - P2 | N=24 | Not yet recruiting | Sponsor: Weill Medical College of Cornell University

New P2 trial • Colorectal Cancer • Gastrointestinal Cancer • Hepatology • Oncology • Solid Tumor • CD8

AGEN1423 Plus Balstilimab With or Without Chemo in Pancreatic Cancer (clinicaltrials.gov) - P2 | N=24 | Not yet recruiting | Sponsor: Bruno Bockorny | Trial completion date: May 2025 ➔ May 2027 | Trial primary completion date: May 2024 ➔ May 2026

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

Study of Dalutrafusp Alfa (Formerly GS-1423) in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=22 | Terminated | Sponsor: Gilead Sciences | Phase classification: P1a/1b ➔ P1

Phase classification • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor

Phase 1 first-in-human study of dalutrafusp alfa, an anti-CD73-TGF-β-trap bifunctional antibody, in patients with advanced solid tumors. (PubMed, J Immunother Cancer) - P1a/1b | "Dalutrafusp alfa doses up to 45 mg/kg Q2W were well tolerated in patients with advanced solid tumors. Additional evaluation of dalutrafusp alfa could further elucidate the clinical utility of targeting CD73-adenosine and TGF-β pathways in oncology."

Journal • Metastases • P1 data • Cardiovascular • Fatigue • Immune Modulation • Immunology • Inflammation • Oncology • Pulmonary Embolism • Respiratory Diseases • Solid Tumor • CD8 • TGFB1

AGEN1423 Plus Balstilimab With or Without Chemo in Pancreatic Cancer (clinicaltrials.gov) - P2 | N=24 | Not yet recruiting | Sponsor: Bruno Bockorny, MD

Combination therapy • New P2 trial • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

Phase 2 trial of AGEN1423, an Anti-CD73-TGFβ-Trap Bifunctional Antibody, in Combination with Balstilimab, with or without Chemotherapy in Subjects with Advanced Pancreatic Cancer (SITC 2022) - "In cohort 2, twelve patients with metastatic PDAC following disease progression on fluorouracil-based therapy will be enrolled to receive AGEN1423 30mg/kg plus balstilimab 3mg/kg on days 1 and 15 of a 28-day cycle in combination with gemcitabine 1000 mg/m2 plus nab-paclitaxel 125 mg/m2 on days 1, 8 and 15 of a 28-day cycle. Biopsies will be obtained at baseline and on-treatment for multiplex immunohistochemistry and additional genomic analyses to better understand changes in the tumor microenvironment following AGEN1423 and balstilimab treatment. Recruitment is anticipated to commence in Q3 2022."

Clinical • Combination therapy • IO biomarker • P2 data • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • NT5E • TGFB1

Agenus Provides Corporate Update and Third Quarter 2022 Financial Report (GlobeNewswire) - "Update on the Phase 2 trial of AGEN1423, an anti-CD73-TGFβ-trap bifunctional antibody in combination with balstilimab (anti-PD-1) in advanced pancreatic cancer will be presented at SITC."

Clinical • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor

Characterization of peripheral biomarkers of GS-1423, a first in class bifunctional anti-CD73-TGFβ receptor II- trap molecule, in a Phase 1 dose escalation study in patients with advanced solid tumors (SITC 2021) - P1a/1b | "Conclusions Blood biomarker analyses of GS-1423 in patients with advanced solid tumors demonstrated undetectable soluble TGFβ1/2/3 and complete TO of CD73 on B and T cells at the 20 mg/kg dose level and above. The mechanism underlying the increase in sCD73 following GS-1423 treatment remains to be elucidated."

Biomarker • Clinical • P1 data • Oncology • Solid Tumor • CD8 • TGFB1

Agenus to Present Botensilimab Data at a Plenary Session of the Society for Immunotherapy of Cancer (SITC) 37th Annual Meeting (GlobeNewswire) - "New data on multiple expansion cohorts from the Phase 1 study of botensilimab (a multifunctional Fc-enhanced anti-CTLA-4) in cold (immunotherapy-resistant) tumors will be presented at an oral plenary session on novel immunotherapies on Saturday, November 12th at 10:50am ET. Three additional presentations will include new data on the mechanisms underpinning botensilimab’s differentiated and enhanced anti-tumor immunity and provide an overview of the Phase 2 trial in progress of AGEN1423, an anti-CD73-TGFβ-trap bifunctional antibody in combination with balstilimab (anti-PD-1) in advanced pancreatic cancer....Separately, Agenus announced today that Dhan Chand, PhD, Head of Drug Discovery at Agenus was selected to present on the topic of enhanced CTLA-4 blockade at the SITC Targets for Cancer IO Deep Dive Series on Wednesday, October 5, from 2:00 pm – 4:00 pm ET."

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

Study of GS-1423 in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1a/1b; N=22; Terminated; Sponsor: Gilead Sciences; Trial completion date: Oct 2021 ➔ Apr 2021; Active, not recruiting ➔ Terminated; The decision to discontinue the study was made based on the totality of the clinical, pharmacokinetic, and pharmacodynamic findings. No safety concerns were observed.

Clinical • Combination therapy • Monotherapy • Trial completion date • Trial termination • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor

Study of GS-1423 in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1a/1b; N=22; Active, not recruiting; Sponsor: Gilead Sciences; Trial completion date: Oct 2026 ➔ Oct 2021

Clinical • Combination therapy • Monotherapy • Trial completion date • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor

Study of GS-1423 in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1a/1b; N=22; Active, not recruiting; Sponsor: Gilead Sciences; Recruiting ➔ Active, not recruiting; N=213 ➔ 22; Trial primary completion date: Oct 2025 ➔ Oct 2020

Clinical • Combination therapy • Enrollment change • Enrollment closed • Monotherapy • Trial primary completion date • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor

Study of GS-1423 in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1a/1b; N=213; Recruiting; Sponsor: Gilead Sciences; Trial completion date: Dec 2024 ➔ Aug 2026; Trial primary completion date: Nov 2021 ➔ Aug 2025

Clinical • Combination therapy • Monotherapy • Trial completion date • Trial primary completion date • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor

Study of GS-1423 in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1a/1b; N=192; Recruiting; Sponsor: Gilead Sciences; Phase classification: P1 ➔ P1a/1b; N=33 ➔ 192; Trial completion date: Jun 2022 ➔ Dec 2024; Trial primary completion date: Jul 2020 ➔ Nov 2021

Clinical • Combination therapy • Enrollment change • Monotherapy • Phase classification • Trial completion date • Trial primary completion date

"#Agenus to Manufacture Clinical Supply of #GS1423 for Gilead $AGEN https://t.co/Kcvvlx3MTP" (@1stOncology)

Clinical

Study of GS-1423 in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1; N=33; Recruiting; Sponsor: Gilead Sciences; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open

Agenus milestone triggers $7.5M payment from Gilead (Agenus Inc. Press Release) - "Agenus...announced today that the FDA has accepted the company's IND filing for AGEN1423 - a milestone in its partnership with Gilead Sciences, Inc. This milestone triggered a cash payment of $7.5M. Agenus is eligible to receive additional milestone payments in 2019 and beyond."

Financing • IND

Agenus closes $150 million immuno-oncology transaction with Gilead (PRNewswire) - "Under the terms of the agreement, Agenus receives $150 million in connection with closing, which includes a $120 million upfront cash payment and a $30 million equity investment. The agreement also includes approximately $1.7 billion in potential future fees and milestones. Gilead received worldwide exclusive rights to AGEN1423. Gilead also received the exclusive option to license two additional programs: AGEN1223 and AGEN2373. Agenus has filed the IND for AGEN1223 and has a planned IND filing for AGEN2373 in the first half of 2019."

IND • Licensing / partnership