On December 12, 2018 Aduro Biotech, Inc. (NASDAQ: ADRO) reported the publication of a peer-reviewed paper in Cell Reports authored by Aduro scientists and Novartis collaborators as part of their ongoing research to study intratumoral stimulator of interferon genes (STING) pathway activation as a potential therapeutic approach for the treatment of cancer (Press release, Aduro Biotech, DEC 12, 2018, View Source;p=RssLanding&cat=news&id=2380389 [SID1234532015]). In this study, researchers determined an intratumoral dosing regimen of STING pathway activator, ADU-S100, optimized for adaptive immunity in mouse models. While high doses of ADU-S100 were effective at clearing injected tumors, researchers found that higher tumor ablative dosing regimens could compromise durable anti-tumor immunity. Lower immunogenic doses of ADU-S100 were shown to optimally elicit CD8+ T cell responses required for systemic and durable anti-tumor immunity, and were also found to be efficacious in combination with checkpoint inhibitor therapy.
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"We previously established that intratumoral STING pathway activation by ADU-S100 results in tumor regression in preclinical models. Our publication in Cell Reports now highlights the importance of optimizing the therapeutic dose regimen for STING agonists with the aim to balance innate and adaptive immune responses triggered by STING activation in the tumor microenvironment," stated Andrea van Elsas, Ph.D. chief scientific officer of Aduro. "Our findings support the use of immunogenic doses of ADU-S100 with checkpoint inhibitors to drive efficacious anti-tumor CD8+ T cell responses. We are encouraged by the potential of ADU-S100 as a novel treatment for cancer as we continue clinical evaluation of our lead compound in combination with checkpoint inhibitors."
The paper titled "Magnitude of Therapeutic STING Activation Determines CD8+ T-Cell Mediated Anti-Tumor Immunity," can be accessed online ahead of the print version in the peer-reviewed Journal Cell Reports.
ADU-S100 is the first STING pathway activator compound to enter the clinic and is currently being evaluated in a Phase 1 clinical trial as a single agent and in combination with ipilimumab (see www.clinicaltrials.gov, identifier NCT02675439) and in a Phase 1b combination trial with spartalizumab (PDR001), Novartis’ investigational anti-PD-1 monoclonal antibody (see www.clinicaltrials.gov, identifier NCT03172936).
About STING Pathway Activator Technology
The Aduro-proprietary STING pathway activator product candidates, including ADU-S100 (MIW815), are synthetic small molecule immune modulators that are designed to target and activate human STING. STING is generally expressed at high levels in immune cells, including dendritic cells. Natural activation of STING is not always sufficient to prevent the growth and spread of cancer cells. In preclinical models, ADU-S100 directly activates STING to further amplify the natural anti-tumor response. Once activated, the STING receptor initiates a profound innate immune response through multiple pathways, inducing the expression of a broad profile of cytokines, including interferons and chemokines. This subsequently leads to the development of a systemic tumor antigen-specific T cell adaptive immune response.
Aduro’s lead molecule, ADU-S100, is the first therapeutic in development specifically targeting STING. In collaboration with Novartis, it is being tested in a Phase 1 clinical trial as a single agent and in combination with ipilimumab, and in a Phase 1b combination trial with spartalizumab (PDR001), an investigational anti-PD-1 monoclonal antibody. These studies are enrolling patients with cutaneously accessible, advanced/metastatic solid tumors or lymphomas. The trials are evaluating the ability of ADU-S100 to activate the immune system and recruit specialized immune cells to attack the injected tumor, leading to a broad immune response that seeks out and kills distant metastases.