On May 12, 2016 Aduro Biotech, Inc. (Nasdaq:ADRO) reported that the first patient has been dosed in a Phase 1 trial for ADU-S100 (also known as MIW815), a novel STING (Stimulator of Interferon Genes) pathway activator (Press release, Aduro BioTech, MAY 12, 2016, View Source [SID:1234512325]). Activation of the STING pathway in tumors has been shown to be a critical step to initiate an innate response that may lead to a systemic adaptive tumor-specific immune response. Novartis, Aduro’s collaborator for STING pathway activator compounds in the field of oncology, is conducting the study. The achievement of this milestone triggers a $35 million milestone payment from Novartis to Aduro.

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"We are thrilled to embark on this landmark Phase 1 study, which we believe is the first clinical trial to specifically target the STING pathway. ADU-S100 (MIW815) has the potential to induce an anti-tumor immune response that is unique to the treated individual, an approach that potentially offers the benefits of a personalized therapy but using an off-the-shelf small molecule," said Thomas Dubensky, Jr., Ph.D., chief scientific officer of Aduro. "ADU-S100 is the first compound to enter the clinic under our collaboration with Novartis, and through this Phase 1 study, we look forward to gaining insight into the safety, tolerability and initial efficacy for several different types of cancer. We have now advanced two differentiated immuno-oncology platforms into the clinic: ADU-S100, with the start of this trial, and our LADD listeria-based immunotherapy strains in clinical studies in multiple indications, including pancreatic, ovarian, lung and prostate cancers, mesothelioma and glioblastoma."

In preclinical models, direct activation of the STING pathway through intratumoral administration of ADU-S100 (MIW815) overcame immune system suppression within the tumor microenvironment, resulting in significant anti-tumor response. These preclinical studies, which were published in Cell Reports, demonstrated that injecting tumors with ADU-S100 (MIW815) induced profound regression of diverse established tumors in mice, both in the injected tumors and distal, untreated lesions. Importantly, treatment of a single tumor initiated a systemically effective T cell response that prevented outgrowth of untreated tumors in other areas of the body (metastases). The ADU-S100-initiated response was durable and provided lasting immunologic memory and anti-tumor protection.

The Phase 1, multicenter, dose escalation study, which includes dose expansion into designated indications, will enroll patients with cutaneously accessible metastatic solid tumors or lymphomas who are in need of other treatment alternatives. The trial is designed to assess the safety, tolerability, pharmacokinetics, pharmacodynamics and anti-tumor activity of ADU-S100 (MIW815). For more information about the clinical trial, please visit www.clinicaltrials.gov and use identifier NCT02675439.

In March 2015, Aduro entered into a collaboration with Novartis for the worldwide research, development and commercialization of novel immuno-oncology products derived from Aduro’s STING pathway activator platform. Under the terms of the agreement, Aduro received $200 million upon signing and an additional $50 million equity investment from Novartis. In addition to the $35 million milestone payment triggered by this Phase 1 trial initiation, Aduro is eligible to receive up to an additional $465 million in development and regulatory milestones if all stated objectives of the collaboration are achieved. Aduro will lead commercialization activities and will book sales in the United States for any products developed and commercialized pursuant to this collaboration, with Novartis leading commercialization activities in all other regions. The companies will share in profits, if any, in the United States, Japan and major European countries, and Novartis will pay Aduro a mid-teens royalty for sales in the rest of the world.

About the Tumor Microenvironment
The tumor microenvironment is the cellular environment in which the tumor exists, and, along with cancerous cells, includes support cells, immune cells, surrounding blood vessels, and the extracellular matrix. The tumor cells and the surrounding microenvironment are closely related and interact constantly. Tumors influence the microenvironment by releasing signals that promote tumor growth, immune tolerance and immune suppression. When tumors initially form, the body’s immune system recruits and activates a host of immune cells to fight the invading tumor. However, in cases where cancer develops, tumors are eventually able to evade the immune system by changing their microenvironment to inhibit the ability of the immune system to recognize and destroy the tumor thus allowing for tumor outgrowth and formation of metastasis.

About STING Pathway Activator Platform
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. 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.