Our STING Program

Silicon Therapeutics has designed first-in-class small molecule STING agonists that show activity across all known isoforms of the human STING protein and demonstrate potent anti-tumor activity in vivo.

Stimulator of Interferon Genes (STING)

STING is a master regulator of type I interferons and a key mediator of innate immunity. Activation of STING provides two critical anti-tumor features:
 
1. The “spark” for initiating a robust innate immune response
2. Enhancement of the adaptive immune response
 
By serving as a bridge between the two arms of the immune system, activation of STING has the potential to transform the tumor microenvironment from immunologically “cold” to “hot” (inflamed), making otherwise resistant tumors respond to checkpoint blockade as well as other T cell targeting immunotherapies.
 
Many preclinical and clinical STING drug discovery programs are based on modifications of the naturally occurring cyclic dinucleotide (CDN) agonists. Due to the short half-life and poor membrane permeability of CDNs, they need to be delivered intratumorally to engage STING in the cytosol. Thus, the benefits of STING activation by these first generation agonists will be limited to only a subset of tumors that are accessible to intratumoral injection.
 
Using our proprietary physics-driven discovery engine, plus cutting-edge capabilities in biology, chemistry, and biophysics, Silicon Therapeutics has developed small molecule agonists of STING that exhibit selective and potent activity across all known isoforms of the human protein. Our compounds induce phosphorylation of STING and IRF3 as well as the expression of type I IFN in primary human immune cells. Our lead series has excellent drug-like properties. When dosed via intravenous administration our small molecule STING agonists show potent anti-tumor activity in mice bearing syngeneic tumors.