On June 22, 2020 Silverback Therapeutics ("Silverback"), a biopharmaceutical company advancing a pipeline of therapies that are systemically delivered but locally active, reported that preclinical data for its lead ImmunoTAC candidate, SBT6050, will be presented at AACR (Free AACR Whitepaper) Virtual Annual Meeting 2020 Session II at 9:00 a.m. ET on June 22, 2020 (Press release, Silverback Therapeutics, JUN 22, 2020, View Source [SID1234561344]).
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The presentation, titled "SBT6050, a HER2-Directed TLR8 ImmunoTAC Therapeutic, is a Potent Human Myeloid Cell Agonist that Provides Opportunity for Single Agent Clinical Activity," shows that TLR8 agonism potently and uniquely activates human myeloid cells, driving a broad spectrum of anti-tumor immune mechanisms, including those not dependent on T cells.
In preclinical studies, SBT6050 activates human myeloid cells in the presence of HER2 expressing tumor cells, resulting in proinflammatory cytokine and chemokine production, inflammasome activation, and the indirect activation of cytolytic activity associated with T and NK cells. SBT6050’s functional profile was not replicated with conjugates comprised of TLR7-specific or resiquimod-derived agonists.
Robust, durable single agent activity is observed with the SBT6050 mouse surrogate in multiple tumor models, including those with low tumor infiltrating lymphocytes. In a human xenograft model lacking T, B, and NK cells, the SBT6050 mouse surrogate is curative as a single agent, demonstrating the ability of myeloid cells to mediate strong anti-tumor activity.
"TLR8’s robust expression and functional profile in human myeloid cells uniquely positions SBT6050 to potentiate anti-tumor responses through the activation of these innate immune cells present in tumors," said Valerie Odegard, Ph.D., Silverback’s chief scientific officer. "Our preclinical data highlight SBT6050’s potential to maximize anti-tumor immune responses, even in tumors lacking T cells. We are excited to be developing a much-needed immunotherapy for patients with HER2-expressing disease and will enter the clinic later this year."