Arcus Therapeutics is a biotechnology company focused on developing innovative cancer therapies by harnessing the body’s immune system. Its research aims to provide novel treatment options for patients.
Arcus Therapeutics Overview
Arcus Therapeutics is a clinical-stage biopharmaceutical company, established in 2015 and headquartered in Hayward, California. Its mission is to “unleash the power of the immune system to conquer cancer” by developing differentiated combination therapies. The company’s approach involves a deep understanding of tumor biology and immunology, creating drug candidates designed for combination treatments. Arcus invests in small molecule, medicinal chemistry, and antibody capabilities to optimize the combinability of molecules within its portfolio.
Arcus accelerates drug development, advancing molecules from initiation to investigational new drug (IND) filing in as little as 18 months. The company’s vision is to become a fully integrated biopharmaceutical company, with in-house capabilities from discovery through commercialization. Strategic partnerships also drive their pursuit of cancer therapies.
Key Immunotherapy Targets
Arcus Therapeutics focuses on several scientific targets within immuno-oncology to modulate the immune system’s response to cancer. TIGIT (T cell immunoreceptor with immunoglobulin and ITIM domain) is an inhibitory receptor on immune cells like T cells and natural killer (NK) cells. It binds to ligands on tumor cells, sending signals that suppress immune activity and allow cancer to evade detection. TIGIT inhibitors block this interaction, removing “brakes” on the immune system and enhancing T cell and NK cell activation to attack cancer. This blockade also reduces the suppressive activity of regulatory T cells (Tregs). Combining TIGIT blockade with other immunotherapies, like PD-1 inhibitors, has shown promise in preclinical studies by enhancing anti-tumor T cell immunity.
Arcus also targets CD73 (ecto-5′-nucleotidase), an enzyme in the adenosine signaling pathway. CD73 converts extracellular AMP into adenosine, which suppresses immune cells like T cells, NK cells, and macrophages. Tumors exploit this to create an immunosuppressive microenvironment. CD73 inhibitors block this enzyme, reducing adenosine levels and allowing for more robust immune cell activation.
Arcus also targets adenosine receptors, A2aR and A2bAR, activated by adenosine in the tumor microenvironment. Elevated adenosine levels in tumors bind to these receptors, inhibiting immune responses and promoting tumor immune escape. Blocking these receptors can restore T cell function and proliferation, enhancing the anti-tumor immune response.
Arcus also addresses the PD-1 (programmed cell death-1) pathway, a well-established immune checkpoint. The PD-1 receptor is expressed on activated T cells, and its ligands, PD-L1 and PD-L2, are often found on tumor cells or within the tumor microenvironment. When PD-1 binds to PD-L1, it sends an inhibitory signal that deactivates T cells, preventing them from attacking cancer cells. Blocking this interaction aims to “reinvigorate” these T cells, allowing them to effectively target and eliminate cancer cells.
Developing Breakthrough Therapies
Arcus Therapeutics develops drug candidates targeting immune pathways for various cancers. Domvanalimab, an Fc-silent anti-TIGIT antibody, is a prominent pipeline asset. This investigational monoclonal antibody blocks TIGIT, freeing immune-activating pathways and enabling immune cells to attack cancer. Domvanalimab is evaluated in combination with other immunotherapies, including zimberelimab, and has shown promising clinical trial results.
In the Phase 3 STAR-221 trial, domvanalimab is investigated with zimberelimab and chemotherapy for upper gastrointestinal adenocarcinomas. Preliminary data from the Phase 2 EDGE-Gastric study indicated a median progression-free survival of 12.9 months with this combination. The ARC-10 study also showed that domvanalimab combined with zimberelimab improved overall survival in patients with PD-L1-high non-small cell lung cancer (NSCLC), demonstrating a 36% reduction in the risk of death compared to zimberelimab alone.
Etrumadenant (AB928) is another key pipeline asset, functioning as a selective dual antagonist of the A2aR and A2bR adenosine receptors. This oral small molecule inhibitor counteracts the immunosuppressive effects of adenosine within the tumor microenvironment. Etrumadenant is currently in Phase 2 clinical development for metastatic colorectal cancer, evaluated in combination with zimberelimab and chemotherapy regimens like m-FOLFOX-6. It continues to be advanced for other solid tumors, including ovarian cancer and NSCLC.
Zimberelimab (AB122) is an anti-PD-1 monoclonal antibody that binds to the PD-1 checkpoint, restoring the anti-tumor activity of T cells. This molecule is evaluated as a foundational anti-PD-1 treatment option in multiple ongoing clinical studies, often in combination with other Arcus molecules like domvanalimab and etrumadenant. Zimberelimab has received approval in China for classical Hodgkin lymphoma and recurrent/metastatic cervical cancer through a partnership with Gloria Biosciences, which holds commercial rights in that region.
Strategic Collaborations
Arcus Therapeutics has forged significant partnerships to accelerate drug development and expand its reach. A prominent collaboration is the 10-year agreement established with Gilead Sciences in May 2020. This partnership involved a capital investment and an equity stake by Gilead, granting Gilead exclusive option rights to Arcus clinical programs.
Under this collaboration, Arcus and Gilead are co-developing four investigational medicines: domvanalimab, zimberelimab, quemliclustat, and etrumadenant. The collaboration expanded to include research targeting inflammatory diseases, in addition to oncology. This strategic alliance streamlines decision-making and leverages the combined expertise of both companies. Arcus also maintains clinical collaborations with AstraZeneca to evaluate novel combinations for cancer treatment.