SEATTLE, Feb. 27, 2019 /PRNewswire/ -- Silverback Therapeutics, Inc., a biotechnology company developing a pipeline of systemically delivered, locally active therapies, will present preclinical data on its lead clinical candidate, SBT6050, at the 110th meeting of the American Association of Cancer Research (AACR), taking place March 29 to April 3 in Atlanta. SBT6050 is a novel immune-modulatory conjugate that utilizes cell surface expression of HER2 to localize activation of TLR8 (toll-like receptor 8) for the treatment of HER2-expressing tumors.
The presentation, titled "A Systemically Administered, Conditionally Active TLR8 Agonist for the Treatment of HER2-Expressing Tumors," is the first data to be presented on Silverback's technology. SBT6050 is comprised of a TLR8 agonist conjugated to a HER2-directed monoclonal antibody, designed to activate myeloid cells only in the presence of HER2-expressing tumor cells with moderate-to-high expression levels. In mouse HER2-expressing tumor models, a surrogate molecule of SBT6050 drives activation of both innate and adaptive immune responses, resulting in single agent efficacy. Due to localized activation of myeloid cells, TLR conjugates do not cause an overproduction of peripheral cytokines in preclinical models. Silverback plans to advance SBT6050 into the clinic in 2020.
"Tumors resistant to checkpoint inhibition lack T cells but are replete with myeloid cells. TLR8 activation of tumor-resident myeloid cells results in potent anti-tumor immune responses, but effective delivery has been the key challenge," said Valerie Odegard, Ph.D., Silverback's chief scientific officer. "Our preclinical studies demonstrate that systemic delivery of a TLR agonist with tumor-localized activity dramatically rewires the tumor microenvironment, resulting in durable, single agent efficacy in tumors refractory to checkpoint blockade."
"These are the first data we are disclosing publicly that demonstrate the ability of Silverback's technology to localize delivery of potent therapies to specific sites in the body," said Peter Thompson, M.D., Silverback's co-founder, chief executive officer and chairman. "Our data show the successful, specific delivery of a TLR agonist to HER2-expressing tumor cells upon systemic administration—thereby addressing a fundamental challenge previously limiting use of innate immune agonists to topical and intratumoral administration, largely due to toxicity arising from widespread myeloid cell activation with systemic use of these agents. With this validating data in hand, we are applying our technology to a broad range of targets and diseases."
Presentation details are as follows:
Presentation Type: Poster (Abstract 3830)
Title: A Systemically Administered, Conditionally Active TLR8 Agonist for the Treatment of HER2-Expressing Tumors
Presenter: Kara Moyes, Ph.D.
Session Date and Time: Tuesday, April 2, 2019 8:00 AM – 12:00 PM
Location: Georgia World Congress Center, Exhibit Hall B
About Silverback's Platform Technology
Silverback's proprietary technology and integrated R&D approach enables the design of product candidates that can be administered systemically, but that act only at the sites of disease. The approach is designed to spare healthy tissues from unwanted side effects, while modifying disease processes in a potent and targeted manner. Silverback is directing the platform to modulate fundamental pathways underlying serious or life-threatening diseases, which traditional antibody and small molecule-based approaches have not been able to successfully target with systemic dosing due to inadequate activity and/or unacceptable toxicities. Silverback has filed over 15 patent families covering the platform and related product candidates.
About Silverback Therapeutics
Silverback Therapeutics is a privately held biotechnology company advancing a pipeline of first-in-class therapies targeting fundamental disease pathways that are systemically delivered but locally active. Enabled by the company's proprietary platform, Silverback's pipeline is rapidly advancing towards clinical studies in several therapeutic areas, including oncology and fibrosis. Since its inception in 2016, Silverback has raised $55 million in venture capital financing from OrbiMed, Celgene Corporation and Alexandria Venture Investments. The company is headquartered in Seattle, Washington. For more information, please visit www.silverbacktx.com.
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