Intra-tumoral Injection of CDN Molecules in Preclinical Models Results in Substantial Regression of Established Tumors, Rejection of Distant, Untreated Metastases and Protection Against Future Tumors
BERKELEY, Calif., May 7, 2015 (GLOBE NEWSWIRE) -- Aduro Biotech, Inc. (Nasdaq:ADRO) today announced two publications in prestigious peer-reviewed journals highlighting the anti-tumor activity of its synthetic cyclic dinucleotide (CDN) molecules when used to treat aggressive metastatic cancers in preclinical models. The journal articles in Cell Reports and in Science and Translational Medicine showcase the ability of Aduro's CDN molecules to specifically target the human STING pathway, which when activated, have been shown to initiate broad innate immune responses that lead to effective and specific adaptive immune responses.
"Having our data peer-reviewed and featured in these major journals is a tremendous validation of our CDN technology and approach to activating the novel STING receptor," said Thomas W. Dubensky, Jr., Ph.D., chief scientific officer for Aduro. "In preclinical animal models, our synthetic CDN molecules potently activate immune stimulating cells including dendritic cells through this central pathway, altering the tumor microenvironment which leads to induction of tumor-specific T cells, durable immune-mediated tumor shrinkage and immune protection when re-challenged with the same tumor cells. In addition, we have shown that our synthetic CDN molecules activate all known variants of human STING receptors. Our ultimate goal with ADU-S100 and other novel CDN candidates is to design compounds that offer an off-the-shelf therapeutic approach to stimulate personalized responses to fight each patient's specific cancer."
The publication, entitled "Direct activation of STING in the tumor microenvironment leads to potent and systemic tumor regression and immunity," is available online in Cell Reports, with the full article available at http://cellreports.cell.com. The researchers demonstrated that injecting tumors with ADU-S100 induced profound regression of established melanoma, colon cancer and breast cancer 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 long-lived immunologic memory and lasting anti-tumor protection.
"Using CDNs to target STING is a unique approach and recent discovery in the immuno-oncology field," said Stephen T. Isaacs, chairman, president and chief executive officer of Aduro. "As announced in March, we are working with Novartis to advance STING-targeted therapies for oncology to use this very powerful mechanism to unlock and activate the immune system to seek and destroy tumor cells in patients."
A second peer-reviewed journal article on Aduro's CDN molecules, entitled "STING agonist formulated cancer vaccines can cure established tumors resistant to PD-1 blockade," was published on April 15, 2015 in Science and Translational Medicine, available here. The data demonstrate that the increased anti-tumor activity of GVAX cancer vaccines formulated with Aduro's CDN molecules was STING-dependent and correlated with increased activation of dendritic cells and antigen-specific CD8+ T cells. In addition, tumors in treated mice showed significant up-regulation of PD-L1. Further, the data showed that the combination therapy of CDN molecules formulated with GVAX cancer vaccines and antibodies blocking the PD-1 immune checkpoint induced significant regression or elimination of established tumors which had not responded to treatment with anti-PD-1 inhibitors alone.
On March 30, 2015, Aduro and Novartis announced a major collaboration to develop the CDN platform targeting the STING pathway for oncology. Under the terms of the agreement, Novartis made an upfront payment of $200 million to Aduro and has committed to paying up to an additional $500 million in development milestones. In addition, Novartis invested $50 million in equity in Aduro. Aduro will lead commercialization activities and will book sales in the U.S., with Novartis leading commercialization in all other regions. The companies will share in profits in the U.S., Japan and major European countries. Novartis will pay Aduro a double digit royalty for sales in the rest of the world.
About Cyclic Dinucleotide (CDN)
Aduro's proprietary CDN product candidates are synthetic small molecule immune modulators that are designed to target and activate a receptor known as the Stimulator of Interferon Genes, or STING. The STING receptor 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 an effective tumor antigen-specific T cell adaptive immune response.
Aduro Biotech, Inc. is a clinical-stage immuno-oncology company focused on the development of technology platforms to stimulate an immune response against cancer. Aduro's lead platform is based on proprietary strains of live-attenuated, double-deleted (LADD) Listeria monocytogenes that induce a potent innate immune response and have been engineered to express tumor-associated antigens to induce tumor-specific T cell-mediated immunity. Aduro has received Breakthrough Therapy designation from the FDA for its lead LADD regimen, CRS-207 in combination with GVAX Pancreas in pancreatic cancer. The company is evaluating the proprietary immuno-oncology combination in the ongoing Phase 2b ECLIPSE clinical trial and has additional ongoing clinical trials with its LADD platform in mesothelioma and glioblastoma. The company is also developing clinical candidates using cyclic dinucleotide (CDN) synthetic small molecule immune modulators that are designed to activate the intracellular STING receptor, a central mediator of the innate immune response. For more information, please visit www.aduro.com.
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This press release contains forward-looking statements for purposes of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include statements regarding our intentions or current expectations concerning, among other things, the potential for our technology, plans and timing of our clinical trials and the potential for eventual regulatory approval of our product candidates. In some cases you can identify these statements by forward-looking words such as "believe," "may," "will," "estimate," "continue," "anticipate," "intend," "could," "would," "project," "plan," "expect" or the negative or plural of these words or similar expressions. Forward-looking statements are not guarantees of future performance and are subject to risks and uncertainties that could cause actual results and events to differ materially from those anticipated, including, but not limited to, our history of net operating losses and uncertainty regarding our ability to achieve profitability, our ability to develop and commercialize our product candidates, our ability to use and expand our technology platforms to build a pipeline of product candidates, our dependence on our lead product candidate, CRS-207, and GVAX Pancreas, our ability to obtain and maintain regulatory approval of our product candidates, our inability to operate in a competitive industry and compete successfully against competitors that have greater resources than we do, our reliance on third parties, and our ability to obtain and adequately protect intellectual property rights for our product candidates. We discuss many of these risks in greater detail under the heading "Risk Factors" contained in the final prospectus from our initial public offering which is on file with the Securities and Exchange Commission. Forward-looking statements are not guarantees of future performance, and our actual results of operations, financial condition and liquidity, and the development of the industry in which we operate, may differ materially from the forward-looking statements contained in this press release. Any forward-looking statements that we make in this press release speak only as of the date of this press release. We assume no obligation to update our forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release.
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