Science & Technology

We are leveraging our proprietary ImmunoTAC^™ technology platform to develop systemically delivered, tissue targeted therapeutics for the treatment of chronic viral infections, cancer, and other serious diseases.

ImmunoTAC^™ PLATFORM

Our ImmunoTAC^™ platform is the result of a focused effort to discover ways to systemically deliver disease-modifying small molecules in a directed fashion to sites of disease.

We are pursuing vital pathways

We are pursuing vital pathways to unlock the potential for numerous therapeutic approaches. Our ImmunoTAC^™ platform is taking us there.

Tumor-Localized Myeloid Cell Activation

We are initially applying our ImmunoTAC^™ platform to create a new class of targeted immuno-oncology agents that direct a myeloid cell activator to the microenvironment in solid tumors to promote cancer cell killing.

Silverback_MOA-illustration_edits_R1V4-Recovered

SBT6050, a HER2-Directed TLR8 ImmunoTAC^™ therapeutic, is designed to be a systemically administered myeloid cell agonist with tumor-localized activity.

The tumor microenvironment (TME) is permeated with myeloid cell populations, including tumor associated macrophages (TAMs), myeloid cell-derived suppressive cells (MDSCs), and conventional dendritic cells (cDCs). When activated or reprogrammed, these cell types orchestrate multiple mechanisms for tumor eradication.

TLR8 is robustly expressed in human myeloid cells prevalent in tumors and not in cell types outside of the myeloid cell lineage, reducing the risk of “off-target” activation. We believe TLR8 is the only innate immune receptor with this profile.

TLR8 activation of myeloid cells produces an anti-tumor innate immune response that includes direct tumor cell killing, recruitment of a diverse array of immune cell subsets, and the reprogramming of immunosuppressive immune cell populations into a productive or pro-inflammatory state.

TLR8 activation of myeloid cells drives a T cell dependent immune response through the enhancement of neoantigen presentation by myeloid cells, recruitment of T cells into the TME, and the production of cytokines that together generate potent, durable anti-tumor immune responses.

SBT6050 drives tumor clearance through an innate immune response, even in the absence of T cells, and activates multiple anti-tumor immune mechanisms.

Solid tumors, including those resistant to T-cell targeted immunotherapies such as PD-1 and CTLA-4 blockade, are permeated with myeloid cells. The activation and reprogramming of myeloid cells result in direct tumor killing and recruitment and activation of additional immune cells. For example, activated myeloid cells are able to amplify T-cell and natural killer (NK)-cell responses – bridging a patient’s innate and adaptive immune systems.

Successful activation of myeloid cells can lead to durable anti-tumor immunity, even in tumors that are resistant to immune checkpoint blockade. Our TLR8 agonist payload is leveraged across SBT6050, SBT6290, and SBT8230. We believe TLR8 is the optimal target for activation and reprogramming of various myeloid cell types due to its potent yet restricted expression and function within such myeloid cells.

SBT8230 is designed to be administered subcutaneously. In the liver, the ASGR1 binding domain engages hepatocytes and the Fc domain of the conjugate binds to the FcgR receptors on myeloid cells. The increase in FcgR binding avidity is a result of ASGR co-binding and results in the internalization of the conjugate into the endo-lysosome where TLR8 resides. SBT8230 directly activates myeloid cells, and these cells in turn activate anti-viral IFNg+ T cell and anti-viral B cell immune responses.

Publications & Posters

SBT8230 (ASGR1-TLR8 ImmunoTAC^™ conjugate for chronic HBV infection)

AASLD 2021
SBT8230, an ASGR1-Directed TLR8 ImmunoTAC^™ Therapeutic for the Treatment of Chronic Hepatitis B Virus, Demonstrates Favorable Preclinical Tolerability With Liver-Localized Activity

AASLD 2020
ASGR1-TLR8, an ASGR1-Directed TLR8 ImmunoTAC^™ Therapeutic, is a Potent Myeloid Cell Agonist with Liver-Localized Activity for the Treatment of Chronic HBV