Arcus Biosciences, Inc. (Arcus) operates as a clinical-stage biopharmaceutical company focused on creating best-in-class therapies.
Using the company's robust and highly efficient drug discovery capability, the company has created a significant portfolio of investigational products, which are in clinical development, with the company's most advanced molecule, an anti-TIGIT antibody, now in multiple Phase 3 registrational studies targeting lung and gastrointestinal cancers. The company's deep po...
Arcus Biosciences, Inc. (Arcus) operates as a clinical-stage biopharmaceutical company focused on creating best-in-class therapies.
Using the company's robust and highly efficient drug discovery capability, the company has created a significant portfolio of investigational products, which are in clinical development, with the company's most advanced molecule, an anti-TIGIT antibody, now in multiple Phase 3 registrational studies targeting lung and gastrointestinal cancers. The company's deep portfolio of novel small molecules and enabling antibodies allows the company to create highly differentiated therapies, which it is developing to treat multiple large indications. The company expects its clinical-stage portfolio to continue to expand and to include molecules targeting immuno-oncology, cancer cell-intrinsic and immunological pathways.
Clinical Product Portfolio
The company has seven clinical programs focused on unique targets, including HIF-2a, TIGIT, PD-1, adenosine A2a and A2b receptors, CD73, CD39, and AXL. In 2020, the company entered into an option, license and collaboration agreement (as amended, the ‘Gilead Collaboration Agreement’) with Gilead to strategically advance its portfolio through a collaborative relationship. The Gilead Collaboration Agreement provides Gilead with an exclusive license to the company's anti-PD-1 program (including zimberelimab) and time-limited exclusive option rights to the company's clinical programs, which they have exercised for the company's anti-TIGIT program (including domvanalimab), adenosine receptor antagonist program (including etrumadenant), and CD73 program (including quemliclustat).
HIF-2a Program
Casdatifan is the company's oral, small-molecule inhibitor of HIF-2a and is its first investigational product against a cancer cell-intrinsic target to enter clinical development. HIF-2a is a protein that is involved in sensing oxygen availability in multiple organs. In certain tumors, HIF-2a activity is highly dysregulated as a result of genetic abnormalities. This creates a situation of pseudohypoxia and the abnormal increase in HIF-2a-mediated expression of a wide array of proteins involved in cancer cell proliferation, survival, treatment resistance, and angiogenesis.
The company's focus for casdatifan is to maximize the opportunity in clear cell renal cell carcinoma (ccRCC) across a variety of settings using a multi-pronged clinical development plan. The initial registrational pathways that the company plans to pursue will focus on combination approaches that build on top of standard of care therapies, while also exploring opportunities for casdatifan to become a foundational standard of care.
The company's development program for casdatifan includes the following:
PEAK-1 is a planned Phase 3 clinical trial to evaluate casdatifan and cabozantinib in ccRCC patients that have received prior immunotherapy, which the company expects to initiate in the second quarter of 2025.
A planned Phase 1b clinical trial that is part of AstraZeneca’s eVOLVE portfolio, where the company expects to evaluate casdatifan and volrustomig (AstraZeneca’s anti-PD-1/anti-CTLA-4 bispecific antibody) in patients with advanced ccRCC who have not received prior immunotherapy (IO-naive setting). Ipilimumab, an anti-CTLA-4 antibody, plus nivolumab, an anti-PD-1 antibody, is approved as a standard of care therapy in first-line ccRCC. The company expects the Phase 1b portion to be initiated by the middle of 2025.
ARC-20 is a Phase 1 clinical trial evaluating casdatifan in multiple cohorts, including cohorts evaluating: casdatifan monotherapy (50 mg, 100 mg, and 150 mg) in late-line ccRCC; casdatifan and cabozantinib in second-line ccRCC; casdatifan plus zimberelimab in first-line ccRCC; casdatifan monotherapy in first-line ccRCC patients with IMDC score of favorable risk; and casdatifan monotherapy in ccRCC patients that have received prior immuno-oncology therapy.
The company recently shared interim data from three cohorts of its ARC-20 study, each evaluating casdatifan monotherapy in ccRCC patients at different doses. At the time of data cut-off (January 3, 2025), the analysis showed that most patients in each cohort (81-87%) experienced disease control with either a partial response or stable disease and were still on treatment. Key highlights from the analysis include an observed 33% response rate in the cohort administering 100 mg of casdatifan once daily and the cohort administering 50 mg of casdatifan twice a day showing a median progression-free survival (mPFS) of 9.7 months (the mPFS for the other cohorts had not been reached at the time of the data cut-off).
Anti-TIGIT Program
TIGIT plays an important role in suppressing the immune response to cancer. The primary ligand for TIGIT (T cell immunoreceptor with Ig and ITIM domains) is CD155, a protein that plays both inhibitory and stimulatory roles in regulating the activity of effector immune cells, such as T and natural killer (NK) cells. TIGIT is an inhibitory receptor highly expressed on T cells displaying an exhausted phenotype, tumor-infiltrating Treg, and NK cells. During the past couple of years, expression of TIGIT, along with PD-1, on precursor exhausted T cells (Tpex), a key population that mediates some of the therapeutic effects of anti-PD-1 agents, has become well documented. The ligands for TIGIT, including CD155, are broadly expressed on multiple cell types in the tumor microenvironment, including cancer cells. CD155 binding to TIGIT results in inhibition of immune cells.
The company is pursuing a broad Phase 2 and Phase 3 development program for domvanalimab in combination with its anti-PD-1 antibody, zimberelimab, in multiple settings, including lung, GI, and head and neck cancers. As described below, each of the company's Phase 3 studies are evaluating domvanalimab with a PD-(L)1 antibody versus the relevant global standard of care. The company estimates that the total addressable market for the ongoing and planned Phase 3 trials of domvanalimab is based on the size of the drug treatable U.S. patient populations.
The company has the following ongoing Phase 3 studies for domvanalimab:
STAR-221 is a Phase 3 study evaluating domvanalimab in combination with zimberelimab and chemotherapy versus nivolumab and chemotherapy in first-line unresectable or metastatic GI cancers.
STAR-121 is a Phase 3 study evaluating domvanalimab in combination with zimberelimab and chemotherapy versus pembrolizumab and chemotherapy in first-line non-small cell lung cancer (NSCLC).
PACIFIC-8 is a Phase 3 study evaluating domvanalimab in combination with durvalumab following chemoradiation in Stage 3 NSCLC, a setting in which durvalumab is already approved.
In addition, the company is evaluating domvanalimab in the following Phase 2 studies:
EDGE-Gastric is a Phase 2 study evaluating the combination of domvanalimab and zimberelimab with and without FOLFOX in GI cancers.
EDGE-Lung is a Phase 2 study evaluating the combination of domvanalimab and zimberelimab with and without quemliclustat and chemotherapy in first- and second-line NSCLC.
VELOCITY-Lung is a Phase 2 study evaluating domvanalimab with and without zimberelimab and sacituzumab govitecan-hziy (Trodelvy) in first- and second-line NSCLC.
Anti-PD-1 Program
The company is evaluating zimberelimab with various intra-portfolio combination partners in many of its ongoing clinical studies. Zimberelimab has been approved in China for classical Hodgkin’s Lymphoma, based on data generated independently by Guangzhou Gloria Biosciences, Co., which owns the commercial rights to zimberelimab in China. As of December 31, 2024, zimberelimab has been evaluated by the company and Gloria Biosciences, either alone or in combination with other agents, in over 2,500 patients.
Adenosine Pathway Programs
Under conditions of cellular damage or cell death, such as in response to certain chemotherapies, large amounts of adenosine triphosphate (ATP) are released into the extracellular environment, where it is converted into adenosine monophosphate by the enzyme CD39 and then into adenosine by the enzyme CD73. The generation of large amounts of extracellular adenosine results in an immunosuppressive response that counteracts some of the potentially beneficial effects of chemotherapy. Two receptors important in mediating the effect of adenosine are A2a, which is expressed on T and NK cells, and A2b, which is co-expressed with A2a on myeloid cells. The company has three clinical programs targeting the adenosine pathway.
CD73 Program
Quemliclustat is a small molecule inhibitor that targets the CD73 enzyme in the ATP-adenosine pathway. The CD73 enzyme plays a critical role in the last step in the conversion of extracellular ATP into adenosine. Targeting CD73 could be a highly effective approach to inhibiting adenosine-mediated immune suppression by suppressing adenosine generation.
In addition to the EDGE-Lung study described above, the company is evaluating quemliclustat in the following studies:
PRISM-1 is a Phase 3 study in metastatic pancreatic cancer evaluating quemliclustat with gemcitabine and nab-paclitaxel (the standard-of-care chemotherapies used for advanced pancreatic cancer) against gemcitabine and nab-paclitaxel.
ARC-8 is a Phase 1b study in metastatic pancreatic cancer evaluating quemliclustat with gemcitabine and nab-paclitaxel (the standard-of-care chemotherapies used for advanced pancreatic cancer) with or without zimberelimab.
Adenosine Receptor Antagonist Program
Etrumadenant is an orally bioavailable small molecule. Unlike most other clinical-stage adenosine receptor antagonists, which only target one of the two receptors, etrumadenant is a highly potent and reversible antagonist of the adenosine A2a and A2b receptors. Consequently, etrumadenant could prove to have more robust anti-tumor effects and activity in a broader range of tumor types than other adenosine A2a or A2b antagonists in clinical development.
The company's studies evaluating etrumadenant are designed to support the potential of etrumadenant in multiple indications that represent substantial market opportunities with significant unmet need. The company is evaluating etrumadenant in its ARC-9 study. ARC-9 is a Phase 2 study evaluating etrumadenant with zimberelimab and FOLFOX, and with and without bevacizumab vs. FOLFOX with and without bevacizumab or regorafenib in second- and third-line metastatic colorectal cancer.
CD39 Program
CD39 is a key enzyme in the adenosine pathway and facilitates the removal of ATP from the tumor microenvironment and its conversion into adenosine. AB598 is the company's anti-CD39 antibody. By targeting the CD39 enzyme, the company intends to increase ATP in the tumor environment, which could, in turn, lead to an enhanced adaptive (T cell) immune response against tumors. The company is evaluating AB598 in its ARC-25 study. ARC-25 is a Phase 1/1b study evaluating AB598 with and without zimberelimab and chemotherapy in gastric cancers.
AXL Program
The AXL receptor tyrosine kinase (AXL) is a transmembrane protein overexpressed in a variety of cancers and certain immune cells. AXL signaling has been implicated in creating an immunosuppressive tumor microenvironment, promoting resistance to chemotherapy and immunotherapy drugs, and is associated with poor prognosis in a variety of cancers. AB801 is the company's AXL inhibitor and is being evaluated in its ARC-27 study. ARC-27 is a Phase 1b study evaluating AB801 with and without chemotherapy in NSCLC.
Early-Stage Drug Discovery Programs
The company has active early-stage discovery efforts focused on the creation of additional development candidates aimed at regulating various aspects of the anti-tumor immune response, as well as other cancer-intrinsic pathways, which it believes play an important role in many human cancers. Casdatifan, quemliclustat, etrumadenant, AB801, and AB598 are all products of the company's internal discovery program. The company is pursuing several new small molecules aimed at modulating key biological pathways in various types of cancer that are responsible for the abnormal growth and resistance to current therapies.
The company also has several active early-stage discovery efforts focused on the discovery of molecules that regulate excessive immune activity in the context of various types of inflammation and autoimmune diseases.
Commercialization Plans
Subject to the timely exercise of Gilead's and Taiho Pharmaceutical Co., Ltd.'s (Taiho) respective option rights discussed below, the Gilead Collaboration Agreement provides the company with a potential commercialization partner for the U.S. and the rest of the world, excluding Japan and certain other Asian countries, and the Option and License Agreement that the company entered into with Taiho (the Taiho Agreement) provides the company with a potential commercialization partner for Japan and certain other Asian countries. For those investigational products being developed in a program that Gilead does not exercise its option to (such as casdatifan), the company expects to have the infrastructure or additional third-party collaborations in place to commercialize such projects with an experienced sales, marketing, and distribution organization. In the U.S., the company has an option to co-promote with Gilead, which it has elected for domvanalimab and zimberelimab. As the company approaches commercialization, it intends to begin building the necessary infrastructure and sales, marketing, and commercial capabilities to co-promote its products, if approved, for the U.S.
Licenses and Collaborations
Gilead Collaboration
Clinical Programs
Under the Gilead Collaboration Agreement, Gilead obtained an exclusive license to develop and commercialize the company's anti-PD-1 program (including zimberelimab) in certain markets and time-limited exclusive options to develop and commercialize any of the company's clinical programs existing at the time of entering into the Gilead Collaboration Agreement and (ii) any programs that enter clinical development during the 10-year collaboration term. Gilead's continued option rights are contingent upon continuation payments on each anniversary of the agreement in 2026 and 2028.
Preclinical Programs
Under the Gilead Collaboration Agreement, Gilead has also received options to two oncology research programs (the Oncology Research Programs) and up to four jointly selected research programs that target inflammatory diseases (the Inflammation Research Programs). The company will lead discovery and early development activities for all Oncology Research Programs and Inflammation Research Programs.
With respect to the Oncology Research Programs, Gilead has the right to exercise its option, on a program-by-program basis, upon the company's completion of certain IND-enabling activities for an option payment.
Taiho License
In 2017, the company entered into the Taiho Agreement pursuant to which Taiho obtained an exclusive option to in-license development and commercialization rights to programs during a five-year term for which IND-enabling studies had begun. These rights are geographically limited to Japan and certain other Asian countries (excluding China) (the Taiho Territory). As of December 31, 2024, Taiho has exercised its option to etrumadenant (the adenosine receptor antagonist program); zimberelimab (the anti-PD-1 program); domvanalimab and AB308 (the anti-TIGIT program); and quemliclustat (the CD73 program). While the five-year term expired in September 2022, Taiho retains option rights to the company's HIF-2a program (including casdatifan) and CD39 program (including AB598). Taiho’s options to these programs expire, on a program-by-program basis, after a prescribed period following the achievement of a clinical development milestone in such program and the company's delivery to Taiho of the requisite data package.
WuXi Biologics License - anti-PD-1
The company's PD-1 license agreement (the WuXi PD-1 Agreement) with WuXi Biologics Ireland Limited (WuXi Biologics), which the company entered into in 2017 and subsequently amended, provides the company with an exclusive license to develop, use, and manufacture products that include an anti-PD-1 antibody, including zimberelimab, throughout the world and commercialize any such products throughout the world except in Greater China.
Under the WuXi PD-1 Agreement, the company is obligated to appoint WuXi Biologics as its exclusive manufacturer of the drug substance for such licensed products for a specified period of time, subject to certain exceptions. The company's sublicensees, however, may manufacture, at any time, certain portions of their requirements for such products, subject to certain conditions. The company made certain covenants not to commercialize any anti-PD-1 antibody licensed or obtained by it after the date of the license agreement with WuXi Biologics, other than anti-PD-1 antibodies licensed from WuXi Biologics, subject to certain exceptions as set forth in the WuXi Agreement.
Abmuno License
In 2016, the company entered into a license agreement (the Abmuno Agreement) with Abmuno Therapeutics LLC (Abmuno) for a worldwide exclusive license to develop, use, manufacture, and commercialize products that include an anti-TIGIT antibody, including domvanalimab.
Strategy
Some of the key elements of the company's strategy include building a differentiated portfolio by focusing on intra-portfolio combinations; designing its clinical trials to advance its compounds as quickly and efficiently as possible; pursuing combinations and indications based on strong biological rationales; and maximizing the value of its portfolio through strategic collaborations and research and development arrangements.
Intellectual Property
As of February 1, 2025, the company's patent estate included over 800 pending or issued patents worldwide, including 32 issued U.S. patents directed to compositions of matter, pharmaceutical compositions, and methods of use for its investigational products and research programs. The company's issued patents and any patents that may issue in the future from its company-owned or licensed pending applications are projected to expire between 2036 and 2044, absent any patent term adjustments or extensions.
Government Regulation
The FDA periodically inspects manufacturing facilities to assess compliance with ongoing regulatory requirements, including current Good Manufacturing Practices (cGMP), which impose extensive procedural, substantive, and record-keeping requirements upon the company and third-party manufacturers engaged by the company if its products are approved.
In the U.S., the company's activities are subject to regulation by various federal, state, and local authorities in addition to the FDA, including but not limited to the Centers for Medicare & Medicaid Services (CMS), other divisions of the U.S. Department of Health and Human Services (HHS), such as the Office of Inspector General, the U.S. Department of Justice (DOJ), and individual U.S. Attorney offices within the DOJ, as well as state and local governments. These laws include, without limitation, the anti-fraud and abuse provisions of the Social Security Act and the false claims laws, each as amended, as applicable.
The Foreign Corrupt Practices Act obligates companies whose securities are listed in the U.S. to comply with accounting provisions requiring the company to maintain books and records that accurately and fairly reflect all transactions of the corporation, including international subsidiaries, and to devise and maintain an adequate system of internal accounting controls for international operations.
In addition to the foregoing, state and federal laws regarding environmental protection and hazardous substances, including the Occupational Safety and Health Act, the Resource Conservation and Recovery Act, and the Toxic Substances Control Act, affect the company's business. These and other laws govern the company’s use, handling and disposal of various biological, chemical and radioactive substances used in, and wastes generated by, the company’s operations.
History
Arcus Biosciences, Inc. was founded in 2015. The company was incorporated in Delaware in 2015.
