STING in Inflammation

STING IN INFLAMMATORY DISEASES

Excessive signaling through STING is linked to a multitude of high unmet need diseases, ranging from broad inflammatory conditions, including systemic lupus erythematosus, rheumatoid arthritis, to interferonopathies, which are a set of rare genetic conditions characterized by interferon overproduction.

A dysregulated type I interferon response may underlie broader autoimmune and inflammatory diseases, for which STING inhibition presents a novel, targeted therapeutic approach. These – among others – include:

    • Systemic lupus erythematosus (SLE): A chronic, occasionally life-threatening, multisystem immune-mediated disorder that affects > 1 million patients in the U.S. A substantial percentage of these patients show elevated cGAS-STING which correlates to increased diseaseactivity.
    • Rheumatoid Arthritis: A chronic inflammatory joint disease that can cause cartilage and bone damage, as well as disability. RheumatoidArthritis affects approximately 1.5 million adults in the U.S. and as of to date no curative therapies exist. Of note, increased cytosolic DNA and cGAS expression have been found in the synoviocytes of RA patients.

Additionally, cGAS-STING signaling is directly implicated in rare monogenic diseases such as Aicardi–Goutières syndrome (AGS) and STING-associated vasculopathy with onset ininfancy (SAVI) among others. These are devastating pediatric diseases where systemic inflammation can lead to encephalopathy or fibrotic lung disease.

There are currently no targeted therapies approved for these patients. As a potential first-in-class STING inhibitor, BBI-10 has the potential to directly address the underlying pathogenesis of these conditions.

BBI-10

Novel, potent, and orally available covalent STING inhibitor with proof-of-mechanism and broad potential to treat inflammatory diseases, as well as rare monogenic disorders.

Learn More About BBI-10

Sources
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4. d’Angelo DM, Di Filippo P, Breda L, Chiarelli F. Type I Interferonopathies in Children: An Overview. Front Pediatr. 2021;9:631329.
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6. An J, Durcan L, Karr RM, et al. Expression of Cyclic GMP-AMP Synthase in Patients With Systemic Lupus Erythematosus. Arthritis Rheumatol (Hoboken, NJ). 2017;69(4):800-807.
7. Prabakaran T, Troldborg A, Kumpunya S, et al. A STING antagonist modulating the interaction with STIM1 blocks ER-to-Golgi trafficking and inhibits lupus pathology. EBioMedicine. 2021;66:103314.
8. Wang J, Li R, Lin H, et al. Accumulation of cytosolic dsDNA contributes to fibroblast-like synoviocytes-mediated rheumatoid arthritis synovial inflammation. Int Immunopharmacol. 2019;76.