Silverback Therapeutics Presents Preclinical Data for SBT8230 at AASLD The Liver Meeting Digital Experience
ASGR1-Directed TLR8 ImmunoTAC Therapeutic is Designed for Liver-Localized Myeloid Activation for the Treatment of Chronic Hepatitis B (cHBV)
SEATTLE--(BUSINESS WIRE)--Silverback Therapeutics, Inc. (“Silverback”) (“the Company”), a clinical-stage biopharmaceutical company leveraging its proprietary ImmunoTAC technology platform to develop systemically delivered and tissue-targeted therapeutics, will present preclinical data for SBT8230 at AASLD The Liver Meeting Digital Experience (November 13-16, 2020). SBT8230 comprises a TLR8 agonist conjugated to an antibody specific for the liver-restricted receptor ASGR1 and is designed to promote functional cures in chronic HBV (cHBV) through potent activation of an anti-viral immune response in a liver-localized manner.
A goal for therapy in cHBV is the achievement of functional cures, defined as sustained loss of Hepatitis B surface antigen (HBsAg) in the blood. Previous studies have shown that interferon-gamma (IFNγ)-skewed anti-viral immune responses can be associated with anti HBsAg seroconversion and functional cures. TLR8 is effective in generating these IFNγ-type immune responses; however, systemic activation by untargeted TLR8 agonists can result in unacceptable toxicities. Therefore, Silverback is developing SBT8230 to achieve liver-localized TLR8 agonism.
In preclinical studies, a TLR8 agonist conjugated to an anti-ASGR1 antibody induced ASGR1-dependent activation of myeloid cells and IFNγ responses. A mouse surrogate of SBT8230 (ASGR1-S) induced anti-HbSAg seroconversion and anti-viral T cell responses, resulting in decreases in viral titers in a mouse model of HBV. ASGR1-S was well tolerated in preclinical studies. These data support the continued preclinical development of SBT8230.
“We believe liver-localized TLR8 agonism is a differentiated approach that could realize the potential of activating a robust anti-HBV immune response and potentially offer durable therapeutic benefit to people with chronic HBV,” said Valerie Odegard, Ph.D., president & chief scientific officer of Silverback Therapeutics. “Seroconversion, together with durable reductions in HBsAg levels and expansion of IFNγ-producing anti-viral T cells, is associated with achievement of functional cures in cHBV. Activation of TLR8 in myeloid cells can induce these responses and the preclinical data for SBT8230 demonstrate the promise of liver-localized myeloid cell activation.”
About Silverback Therapeutics
Silverback Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on leveraging its proprietary ImmunoTAC technology platform to develop systemically delivered and tissue targeted therapeutics for the treatment of cancer and other serious diseases. Silverback’s platform enables the strategic pairing of proprietary payloads that modulate key disease modifying pathways with monoclonal antibodies directed at specific disease sites. Initially, Silverback is creating a new class of targeted immuno-oncology agents that direct a TLR8 agonist myeloid cell activator to the tumor microenvironment in solid tumors to promote cancer cell killing. Silverback’s lead product candidate, SBT6050, is a therapeutic comprised of a TLR8 agonist payload conjugated to a HER2-directed monoclonal antibody that targets tumors such as certain breast, gastric and non-small cell lung cancers. SBT6050 is currently in a Phase 1 clinical study in patients with advanced or metastatic HER2-expressing solid tumors. SBT6290 is our second product candidate, expanding on the potential of a TLR8 agonist as a payload. SBT6290 is a TLR8 linker-payload conjugated to a monoclonal antibody that targets Nectin4, which is expressed in certain bladder, triple negative breast, head and neck, and non-small cell lung cancers. Silverback’s lead virology program, SBT8230, is an ImmunoTAC therapeutic engineered to potently activate human myeloid cells in the liver for the treatment of cHBV. Silverback Therapeutics is located in Seattle, Washington. To learn more, visit www.silverbacktx.com.
Steve E. Kunszabo