ralzapastotug (AB308) / Arcus Biosci, Gilead, Otsuka - LARVOL DELTA

A Study to Evaluate AB308 in Combination With AB122 in Participants With Advanced Malignancies (clinicaltrials.gov) - P1 | N=94 | Completed | Sponsor: Arcus Biosciences, Inc. | Active, not recruiting ➔ Completed

Trial completion • B Cell Lymphoma • Cervical Cancer • Diffuse Large B Cell Lymphoma • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Hematological Malignancies • Lung Cancer • Lymphoma • Melanoma • Multiple Myeloma • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

A Study to Evaluate AB308 in Combination With AB122 in Participants With Advanced Malignancies (clinicaltrials.gov) - P1 | N=94 | Active, not recruiting | Sponsor: Arcus Biosciences, Inc. | Trial completion date: Jan 2025 ➔ Sep 2025 | Trial primary completion date: Jan 2025 ➔ Sep 2025

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Cervical Cancer • Diffuse Large B Cell Lymphoma • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Hematological Disorders • Hematological Malignancies • Lung Cancer • Lymphoma • Melanoma • Multiple Myeloma • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

A Study to Evaluate AB308 in Combination With AB122 in Participants With Advanced Malignancies (clinicaltrials.gov) - P1 | N=94 | Active, not recruiting | Sponsor: Arcus Biosciences, Inc. | Trial completion date: Jan 2024 ➔ Mar 2025 | Trial primary completion date: Jan 2024 ➔ Mar 2025

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Cervical Cancer • Diffuse Large B Cell Lymphoma • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Hematological Disorders • Hematological Malignancies • Lung Cancer • Lymphoma • Melanoma • Multiple Myeloma • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

Fc-silent anti-TIGIT antibodies potentiate anti-tumor immunity without depleting regulatory T cells (SITC 2023) - P1 | "The ability of human TIGIT-specific clinical antibodies that are Fc-silent (domvanalimab) or Fc-enabled (AB308) to promote NK-mediated antibody-dependent cell-mediated cytotoxicity (ADCC) was evaluated using an in vitro co-culture system and by measuring absolute T cell counts in longitudinal peripheral blood patient samples from Phase 1 dose escalation clinical trials NCT03628677 and NCT04772989. Anecdotal clinical outcomes in two patients from NCT03628677 receiving domvanalimab in combination with an anti-PD-1 antibody, zimberelimab, are also reported...Conclusions We demonstrate that Fc-silent anti-TIGIT antibodies potentiate activation of tumor-specific T cells and anti-tumor efficacy without depleting Treg (figure 1). These data provide critical insights related to activity of anti-TIGIT antibodies lacking Fc functionality, such as domvanalimab."

IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD226 • CD4 • CD8 • TIGIT

A Study to Evaluate AB308 in Combination With AB122 in Participants With Advanced Malignancies (clinicaltrials.gov) - P1 | N=94 | Active, not recruiting | Sponsor: Arcus Biosciences, Inc. | Recruiting ➔ Active, not recruiting | Trial completion date: Jul 2025 ➔ Jan 2024 | Trial primary completion date: Jul 2025 ➔ Jan 2024

Combination therapy • Enrollment closed • Metastases • Trial completion date • Trial primary completion date • Cervical Cancer • Diffuse Large B Cell Lymphoma • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Hematological Disorders • Hematological Malignancies • Lung Cancer • Lymphoma • Melanoma • Multiple Myeloma • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Oncology

A Study to Evaluate AB308 in Combination With AB122 in Participants With Advanced Malignancies (clinicaltrials.gov) - P1 | N=107 | Recruiting | Sponsor: Arcus Biosciences, Inc. | Trial completion date: Dec 2023 ➔ Jul 2025 | Trial primary completion date: Jun 2023 ➔ Jul 2025

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Cervical Cancer • Diffuse Large B Cell Lymphoma • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Hematological Disorders • Hematological Malignancies • Lung Cancer • Lymphoma • Melanoma • Multiple Myeloma • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

Taiho Pharmaceutical Enters into a Clinical Trial Agreement with Arcus Biosciences and Gilead Sciences (Taiho Press Release) - "Taiho Pharmaceutical...announced today that it has entered into a Clinical Trial Agreement with Arcus Biosciences, Inc. ('Arcus') and Gilead Sciences, Inc. ('Gilead') related to the Arcus programs which Taiho had previously obtained rights to develop and commercialize in Japan and certain other territories in Asia (excluding China)....These optioned programs currently are the anti-TIGIT program (domvanalimab and AB308), the anti-PD-1 monoclonal antibody program (zimberelimab), and the adenosine receptor antagonist program (etrumadenant). The Clinical Trial Agreement is expected to further accelerate the development of these Arcus in-licensed products in Japan. Taiho will participate in two global phase 3 clinical trials, STAR-121 trial in non-small cell lung cancer, and STAR-221 trial in upper gastrointestinal tract cancer, both of which are expected to be initiated in Japan during 2023."

Licensing / partnership • New P3 trial • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer

A Study to Evaluate AB308 in Combination With AB122 in Participants With Advanced Malignancies (clinicaltrials.gov) - P1 | N=107 | Recruiting | Sponsor: Arcus Biosciences, Inc. | N=160 ➔ 107

Combination therapy • Enrollment change • Metastases • Cervical Cancer • Diffuse Large B Cell Lymphoma • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Hematological Disorders • Hematological Malignancies • Lung Cancer • Lymphoma • Melanoma • Multiple Myeloma • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

[VIRTUAL] ARC-12: Phase I/Ib dose escalation and dose expansion study to evaluate the safety and tolerability of AB308 + zimberelimab (AB122) in advanced malignancies (ESMO 2021) - P1 | "Additional secondary endpoints in the dose-expansion are disease control rate and duration of response. ARC-12 is actively recruiting in the USA (NCT04772989)."

Clinical • P1 data • Oncology • Solid Tumor • TIGIT

ARC-12: Phase 1/1b Study to Evaluate Safety and Tolerability of AB308 + Zimberelimab (AB122) in Advanced Malignancies (ASH 2021) - P1 | "Safety and efficacy data will be analyzed using summary statistics and Kaplan Meier estimates as appropriate; PK parameters will be estimated using noncompartmental methods. ARC-12 is actively recruiting at sites in the United States (NCT04772989)."

Clinical • P1 data • Bone Marrow Transplantation • Cervical Cancer • Diffuse Large B Cell Lymphoma • Gastrointestinal Cancer • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Lung Cancer • Lymphoma • Melanoma • Multiple Myeloma • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • Transplantation • TIGIT

"@ScotsKnight2 @AstraZeneca @ultragenyx Big pharmas #TIGIT deals! EOS-448 @GSK → $ITOS $2B AGEN1777 @ScienceAtBMS → $AGEN $1.56B Ociperlimab @Novartis → $BGNE $1B AB308 @GileadSciences → $RCUS $700M Etiqilimab @MereoBioPharma $MREO owns 100%: no value on current MC" (@ej23ny)

TIGIT

Anti-TIGIT antibodies promote immune activation relevant to targeting stem-like and tumor-specific T cells in combination with anti-PD-1 (IMMUNOLOGY 2022) - "In mice, while combining Fc-silent or Fc-enabled anti-mouse TIGIT antibody with anti-PD-1 resulted in greater tumor growth inhibition than with anti-PD-1 alone, the activity of Fc-enabled anti-TIGIT was associated with intratumoral Treg depletion. These data provide a rationale for combination with immune-activating agents and support ongoing clinical evaluation of AB154 and AB308 with biomarker strategies focused on understanding the role of Fc functionality."

Combination therapy • IO biomarker • Oncology • CD8 • PVR • TIGIT

Arcus Biosciences Reports Fourth Quarter and Full-Year 2021 Financial Results and Provides Corporate Update (Businesswire) - "2022 Milestones: (i) Presentation of initial data from the Phase 1/1b ARC-12 study evaluating AB308, an Fc-enabled anti-TIGIT antibody, in combination with zimberelimab in advanced malignancies; (ii) Data from the etrumadenant-containing arm of ARC-7 are anticipated to be presented in 2H22."

P1 data • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Arcus Biosciences Provides Update on Clinical Programs, Including Key 2022 Milestones (Businesswire) - "Anti-TIGIT program (domvanalimab and AB308): Anticipated 2022 Milestones: Data from ARC-7, an ongoing randomized 150-patient three-arm study in first-line PD-L1≥50% NSCLC, including progression-free survival data, are expected to be presented in 2H22. In addition to ARC-10, an ongoing registrational study in 1L PD-L1≥50% NSCLC, we and Gilead plan to initiate two new Phase 3 studies in lung and gastrointestinal (GI) cancers, as well as additional clinical studies of domvanalimab-based combinations, in 2022. AstraZeneca and Arcus will initiate the PACIFIC-8 registrational Phase 3 study in January to evaluate domvanalimab plus durvalumab, an anti-PD-L1 antibody, in unresectable Stage 3 NSCLC with curative intent, where durvalumab is standard of care. Data from the Phase 1/1b ARC-12 study evaluating AB308, an Fc-enabled anti-TIGIT antibody, plus zimberelimab in advanced malignancies will inform future development plans."

Clinical data • New P3 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology

Gilead and Arcus Biosciences Complete Closing of Option Exercise for Three Clinical-Stage Programs and New Research Collaboration (Businesswire) - "Gilead Sciences...and Arcus Biosciences...announced the closing of Gilead’s option exercises to three programs in Arcus’s clinical-stage portfolio and a new research collaboration between the two companies. On November 17, 2021, Gilead exercised its options to anti-TIGIT molecules domvanalimab and AB308, as well as clinical candidates etrumadenant (dual adenosine A2a/A2b receptor antagonist) and quemliclustat (small molecule CD73 inhibitor)....Under the terms of the parties’ Option, License and Collaboration Agreement,...the closing of this transaction triggers option payments totaling $725 million from Gilead to Arcus, expected to be paid in early Q1 2022."

Financing • Licensing / partnership • Oncology

Taiho Pharmaceutical Exercises Option for an Exclusive License to Arcus Biosciences’ Anti-TIGIT Program in Japan and Certain Territories in Asia (Businesswire) - "Arcus Biosciences, Inc...and Taiho Pharmaceutical Co., Ltd...announced that Taiho exercised its option for anti-TIGIT antibodies domvanalimab (development code: AB154) and AB308 from Arcus Biosciences ('Arcus'), in Japan and certain other territories in Asia (excluding China). This option exercise is based on an option and license agreement between Taiho and Arcus contracted in September 2017...Through this collaboration, Taiho will further support the development and commercialization of domvanalimab and will continue its mission to deliver innovative drugs to patients and medical professionals."

Licensing / partnership • Lung Cancer • Non Small Cell Lung Cancer • Oncology

AB308 is an Anti-TIGIT Antibody That Enhances Immune Activation and Anti-tumor Immunity Alone and in Combination with Other I-O Therapeutic Agents (SITC 2021) - "Concurrent blockade of multiple immune checkpoints has the potential to confer effective and durable responses in the treatment of cancer. The data presented here support the clinical use of AB308 and provides a rationale for combination with zimberelimab and adenosine pathway blocking agents such as etrumadenant and CD73 small molecule inhibitor, AB680."

Combination therapy • Oncology • CD4 • CD73 • CD8 • ENTPD1 • ITGAE • TIGIT

Gilead Exercises Options to Three Arcus Biosciences Clinical-Stage Programs and Adds Research Collaboration (GlobeNewswire) - "Gilead Sciences, Inc...and Arcus Biosciences, Inc...announced that Gilead has exercised its options to three programs in Arcus’s clinical-stage portfolio, including both anti-TIGIT molecules, domvanalimab and AB308, as well as etrumadenant and quemliclustat...The parties expect the transaction to close by year-end...Under the terms of the parties’ Option, License and Collaboration Agreement (the '2020 Agreement'), for the three options that Gilead is exercising today, Arcus will receive option payments totaling $725 million....Arcus may be required to operationalize at least 50% of the clinical studies, with costs to be shared by Gilead and Arcus. The royalties payable by Gilead to Arcus on sales for these three programs outside of the U.S. were slightly reduced. The reduced royalties range from the mid-teens to the low twenties....Upon closing of the transaction for all three programs, the $100 million option continuation payment due in 2022 will not be made by Gilead."

Licensing / partnership • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Prostate Cancer

Arcus Biosciences Reports Second Quarter 2021 Financial Results and Provides Operational Highlights (Businesswire) - "Upcoming Milestones: (i) AB308: Initiation of five expansion cohorts in the Phase 1b portion of the study is expected in the third quarter; (ii) Initiation of clinical development for our HIF-2α inhibitor, AB521, is anticipated to occur in 4Q21. This first study is expected to be in healthy volunteers to expeditiously characterize the pharmacokinetic and safety profile of AB521 and to identify the starting dose for the Phase 1/1b study in oncology indications, which is anticipated to begin in 1H22."

New P1 trial • Trial status • Cervical Cancer • Esophageal Cancer • Gastric Cancer • GastroEsophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Gynecologic Cancers • Hematological Malignancies • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology

A Study to Evaluate AB308 in Combination With AB122 in Participants With Advanced Malignancies (clinicaltrials.gov) - P1; N=154; Recruiting; Sponsor: Arcus Biosciences, Inc.; Not yet recruiting ➔ Recruiting

Enrollment open • Cervical Cancer • Diffuse Large B Cell Lymphoma • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Hematological Disorders • Hematological Malignancies • Lung Cancer • Lymphoma • Melanoma • Multiple Myeloma • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • PD-L1

A Study to Evaluate AB308 in Combination With AB122 in Participants With Advanced Malignancies (clinicaltrials.gov) - P1; N=154; Not yet recruiting; Sponsor: Arcus Biosciences, Inc.

Clinical • Combination therapy • New P1 trial • Cervical Cancer • Diffuse Large B Cell Lymphoma • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Hematological Disorders • Hematological Malignancies • Lung Cancer • Lymphoma • Melanoma • Multiple Myeloma • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor