AB598 / Arcus Biosci - LARVOL DELTA

Exogenous ATP drives transcriptomic changes related to DC activation that are elevated by neoadjuvant chemoradiotherapy in esophageal cancer (SITC 2025) - "Here we report on the development of an ATP signature and its application in assessing the effects of eATP-elevating therapies.Methods Monocyte-derived dendritic cells (moDCs) were exposed to combinations of A549 cells, docetaxel, AB598 or its isotype control, and ATP, followed by RNA-sequencing...In parallel, the relationship between PD-L1 mRNA levels and DC abundance, assessed by lineage genes, was evaluated in TCGA gastroesophageal (GEC) datasets.1 The effects of ICD chemotherapy on DC abundance and ATP signature were evaluated in data from 24 patients in the PERFECT trial,2 which evaluated neoadjuvant carboplatin, paclitaxel, and concurrent radiotherapy (CROSS) with atezolizumab in resectable esophageal cancer (ESCA).Results By comparing mRNA from moDCs cultured with exogenous ATP in the presence or absence of AB598, we derived a 23-gene ATP signature...Analysis of TCGA GEC patients revealed lower expression of DC lineage genes in PD-L1 low patients.1 Expression of..."

Clinical • IO biomarker • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Oncology • ENTPD1 • PD-L1

Tumor Biomarker Analysis of Anti-CD39 Monoclonal Antibody AB598 in a First-In-Human Phase I Trial in Patients with Advanced Solid Tumors (SITC 2025) - P1 | "ARC-25 (NCT05891171) is a phase 1/1b trial to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of AB598 monotherapy and combination therapy with zimberelimab (anti-PD-1) and standard-of-care chemotherapy. Enrollment at any clinical study site did not begin prior to that site receiving approval from the ethics committee of record for the protocol and all materials provided to potential patients. All participants provided informed consent prior to any clinical research sample collection."

Biomarker • Clinical • First-in-human • IO biomarker • Metastases • P1 data • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor • ENTPD1

Peripheral pharmacodynamic analysis of anti-CD39 monoclonal antibody AB598 in a first-in-human phase I trial in patients with advanced solid tumors (SITC 2025) - P1 | "ARC-25 (NCT05891171) is an ongoing phase 1/1b first-in-human trial to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and clinical activity of both AB598 monotherapy and AB598 in combination with zimberelimab (anti-PD1) and mFOLFOX chemotherapy in patients with advanced solid tumors.Methods Here we present peripheral PD data from AB598 monotherapy dose escalation cohorts (31 subjects dosed at 300, 900, 1800, or 3000 mg Q3W). Enrollment at any clinical study site did not begin prior to that site receiving approval from the ethics committee of record for the protocol and all materials provided to potential patients. All participants provided informed consent prior to any clinical research sample collection."

Clinical • First-in-human • IO biomarker • Metastases • P1 data • PK/PD data • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor • ENTPD1

Clinical pharmacokinetic/pharmacodynamic relationship for AB598, a large molecule inhibitor of CD39 (AACR-NCI-EORTC 2025) - P1 | "AB598 is under investigation in a first-in-human, multicenter, non-randomized, open-label phase 1 study in patients with advanced solid tumors (NCT05891171).Objective· To characterize the pharmacokinetics (PK) of AB598 in cancer patients · To describe the relationship between AB598 PK and tumor pharmacodynamic (PD) markers (receptor occupancy and enzymatic inhibition) to inform the selection of an appropriate dose for future clinical trials.Methods· The study consists of two phases: a monotherapy AB598 dose escalation phase (300 mg, 900 mg, 1800 mg and 3000 mg IV Q3W) that is complete, and an ongoing combination dose expansion phase (AB598 + FOLFOX + zimberelimab)...· AB598 half-life is consistent with other anti-CD39 antibodies. · 2000 mg IV Q2W observed concentrations adequately achieve the target effective concentrations."

Clinical • PK/PD data • Oncology • Solid Tumor • ENTPD1

ARC-25: Study of AB598 Monotherapy and Combination Therapy in Participants With Advanced Cancers (clinicaltrials.gov) - P1 | N=40 | Active, not recruiting | Sponsor: Arcus Biosciences, Inc. | Recruiting ➔ Active, not recruiting | N=87 ➔ 40

Enrollment change • Enrollment closed • Monotherapy • Bladder Cancer • Breast Cancer • Cervical Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Genito-urinary Cancer • Head and Neck Cancer • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • HER-2

Inhibition of CD39 by AB598 enhances the effects of chemotherapy and anti-PD-1 therapy to promote myeloid cell and T cell anti-tumor immunity (AACR 2025) - "AB598 is a novel, humanized, Fc-silent anti-CD39 therapeutic antibody that inhibits CD39 enzymatic activity with sub-nanomolar potency and is currently being evaluated in ARC-25, a Phase 1/1b clinical trial in subjects with gastric cancer, in combination with FOLFOX and zimberelimab, an anti-PD-1 antibody...Immunophenotyping of both tumor and tumor-draining lymph nodes demonstrated that myeloid cells and T cells were activated as a result of AB598 treatment. In conclusion, the co-culture in vitro and murine in vivo data support the combination of AB598 with the standard of care agents oxaliplatin and anti-PD-1 to enhance myeloid cell and T cell activation to drive anti-tumor immunity."

IO biomarker • Gastric Cancer • Oncology • Solid Tumor • ENTPD1

ARC-25: Study of AB598 Monotherapy and Combination Therapy in Participants With Advanced Cancers (clinicaltrials.gov) - P1 | N=87 | Recruiting | Sponsor: Arcus Biosciences, Inc. | Trial completion date: Aug 2025 ➔ Mar 2026 | Trial primary completion date: Aug 2025 ➔ Mar 2026

Combination therapy • Metastases • Monotherapy • Trial completion date • Trial primary completion date • Bladder Cancer • Breast Cancer • Cervical Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Genito-urinary Cancer • Head and Neck Cancer • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • HER-2

Characterization of AB598, a CD39 Enzymatic Inhibitory Antibody for the Treatment of Solid Tumors. (PubMed, Mol Cancer Ther) - "In cynomolgus monkeys, systemically dosed AB598 results in effective enzymatic inhibition in tissues, full peripheral and tissue target engagement, and a reduction in cell surface CD39 both in tissues and in the periphery. Taken together, these data support a promising therapeutic strategy of harnessing the eATP generated by standard-of-care chemotherapies to prime the tumor microenvironment for a productive anti-tumor immune response."

Journal • Oncology • Solid Tumor • ENTPD1

Inhibition of CD39 by AB598 increases extracellular ATP resulting in activation of myeloid cells and T cells to enhance anti-tumor immunity (AACR 2024) - "AB598 significantly enhanced T cell activation in the presence of chemotherapy. These data demonstrate that using AB598 results in elevated eATP, which boosts immune cell activation to promote anti-tumor immunity."

Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CD83 • CD86 • ENPP1 • ENTPD1

Arcus Biosciences Reports Third Quarter 2023 Financial Results and Provides a Pipeline Update (Businesswire) - "Early Clinical and Preclinical Programs: (i) ARC-25, a Phase 1 trial in cancer patients for AB598, an anti-CD39 antibody, is currently enrolling; (ii) Arcus initiated a Phase 1 study in healthy volunteers of AB801, its potent and highly selective AXL inhibitor, and expects to initiate a Phase 1 study in advanced cancer patients in the first quarter of 2024."

Trial status • Solid Tumor

AB598, a CD39 inhibitory antibody, promotes immune-mediated tumor control (SITC 2023) - "This study provides a rationale for combining CD39 inhibition with chemotherapy that induces ATP release and checkpoint inhibition in clinical settings. AB598 is currently in a Phase 1 trial in advanced cancer patients."

IO biomarker • Oncology • Solid Tumor • ENTPD1

Study of AB598 Monotherapy and Combination Therapy in Participants With Advanced Cancers (clinicaltrials.gov) - P1 | N=81 | Recruiting | Sponsor: Arcus Biosciences, Inc. | Trial completion date: Nov 2025 ➔ Aug 2025 | Trial primary completion date: Nov 2025 ➔ Aug 2025

Combination therapy • Metastases • Monotherapy • Trial completion date • Trial primary completion date • Bladder Cancer • Breast Cancer • Cervical Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • HER-2

Arcus Biosciences Reports Second-Quarter 2023 Financial Results and Provides a Pipeline Update (Businesswire) - "AB521 (HIF-2a inhibitor)...Initial pharmacokinetic (PK), pharmacodynamic (PD) and safety data, along with any preliminary signs of anti-tumor activity from the dose-escalation phase of ARC-20, are expected in late 2023 or early 2024. Efficacy data from the dose-expansion stage of the ARC-20 study are anticipated later in 2024. A Phase 2 study evaluating AB521 in combination with other agents is anticipated to begin in the fourth quarter of 2023....Early Clinical and Preclinical Programs: Arcus initiated ARC-25, a Phase 1 trial in cancer patients for AB598, its anti-CD39 antibody, in the second quarter of 2023. Arcus expects to initiate a Phase 1 study in healthy volunteers of AB801, its potent and highly selective Axl inhibitor, in the third quarter of 2023."

New P2 trial • P1 data • Trial status • Bladder Cancer • Breast Cancer • Cervical Cancer • Clear Cell Renal Cell Carcinoma • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Genito-urinary Cancer • Gynecologic Cancers • Head and Neck Cancer • Kidney Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer

Study of AB598 Monotherapy and Combination Therapy in Participants With Advanced Cancers (clinicaltrials.gov) - P1 | N=81 | Recruiting | Sponsor: Arcus Biosciences, Inc. | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Metastases • Monotherapy • Bladder Cancer • Breast Cancer • Cervical Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • Urothelial Cancer • HER-2

Study of AB598 Monotherapy and Combination Therapy in Participants With Advanced Cancers (clinicaltrials.gov) - P1 | N=81 | Not yet recruiting | Sponsor: Arcus Biosciences, Inc.

Combination therapy • Metastases • Monotherapy • New P1 trial • Bladder Cancer • Breast Cancer • Cervical Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • Urothelial Cancer • HER-2

Arcus Biosciences Reports First Quarter 2023 Financial Results and Provides a Pipeline Update (Businesswire) - "Pipeline Highlights: Preclinical Programs - (i) The IND for AB598, Arcus’s anti-CD39 antibody, has been cleared by the FDA, and Arcus is on track to initiate a Phase 1 trial in cancer patients in the second quarter of 2023; (ii) Arcus expects to initiate a Phase 1 study for AB801, a potent and highly selective Axl inhibitor, in the second half of 2023. Arcus presented data at the American Association for Cancer Research (AACR) Annual Meeting in April 2023 demonstrating high potency and selectivity of AB801 for Axl over other kinases in multiple assays; the data also showed that AB801 significantly decreased tumor volume and increased survival in mouse tumor models."

IND • New P1 trial • Preclinical • Oncology

Characterization of AB598, a therapeutic anti-human CD39 antibody for the treatment of cancer (AACR 2023) - "When used in combination with an ICD-inducing chemotherapy agent, AB598 can promote anti-tumor immunity by activation of myeloid cells due to increased local ATP levels. Preclinical characterization of the pharmacodynamic effects of AB598 support our therapeutic rationale and demonstrate target engagement and inhibition both peripherally and intratumorally."

Oncology • ENTPD1

AB598, a therapeutic anti-human CD39 antibody, binds and inhibits CD39 enzymatic activity in vivo to promote anti-tumor immunity (SITC 2022) - "Results Real-time measurement of ATP showed the ability of oxaliplatin to induce ATP release in MC38 tumor cells in vitro . Relative percentages of the immune cells in the lymph nodes were unaffected, suggesting internalization or downregulation, not cellular depletion, as the mechanism for the decrease in cell-surface CD39. Conclusions Our results indicate the superb ability of AB598 to inhibit enzymatic activity and tumor growth in vivo and provide a rationale for the combination of CD39 inhibition with ICD-inducing chemotherapy in the clinic."

IO biomarker • Preclinical • Oncology • Solid Tumor • ENTPD1

Arcus Biosciences Reports Third Quarter 2022 Financial Results and Provides a Pipeline Update (Businesswire) - "Arcus remains on track to initiate a Phase 1 trial in cancer patients for AB598, its anti-CD39 antibody, in the first half of 2023. Arcus expects to initiate a Phase 1 trial in 2023 for its next small molecule program, AB801, a potent and highly selective Axl inhibitor."

Enrollment status • Oncology • Solid Tumor

Arcus Biosciences Reports Second Quarter 2022 Financial Results and Provides a Pipeline Update (Businesswire) - "Arcus is on track to initiate ARC-20, a Phase 1/1b study to explore the safety and clinical activity of AB521 in cancer patients in Q3 2022…. AB598 (anti-CD39 antibody) continues to progress through preclinical development, and we expect to file an Investigational New Drug (IND) application and initiate a Phase 1 trial in cancer patients in the first half of 2023…. As part of Arcus’s and Gilead’s research collaboration, the companies have now selected targets for the two drug discovery programs in oncology. Upon completion of certain IND-enabling activities, Gilead has the right to exercise its option for a payment of $60 million for each program.”"

Financing • IND • New P1 trial • P1 data • Oncology

Inhibition of CD39 results in elevated ATP and activation of myeloid cells to promote anti-tumor immunity (AACR 2022) - "In human macrophages treated with ATP, AB598 activates the inflammasome, resulting in the secretion of pro-inflammatory IL-18 and IL-1β. The ATP-dependent effects of AB598 support a therapeutic rationale of combining it with immunogenic therapies that induce release of ATP, such as chemotherapy and radiation, which might represent a new paradigm in the treatment of advanced solid tumors."

Oncology • Solid Tumor • CD14 • CD86 • ENTPD1 • IL18 • IL1B

Arcus Biosciences Reports Fourth Quarter and Full-Year 2021 Financial Results and Provides Corporate Update (Businesswire) - "Discovery Programs: Recent Updates: Arcus recently selected AB598 (CD39 antibody) as a development candidate, which is advancing into IND-enabling studies; several other oncology discovery programs continue to progress."

Pipeline update • Oncology