Our Science

STAT3 is a key regulatory protein positioned at the intersection of many signaling pathways integral to the survival and immune evasion of cancer cells as well as to the pathogenesis of many inflammatory and fibrotic diseases.

Cancer

STAT3 has long been recognized as a prime target for oncology. Given the integral role of STAT3 in both tumorigenesis and immune suppression, inhibition of STAT3 signaling is expected to have a synergistic therapeutic effect on cancer cells.

Tvardi has developed TTI-101, an orally delivered, small molecule, direct inhibitor of STAT3. TTI-101 has demonstrated efficacy in a variety murine tumor models including head and neck, lung, breast, and liver cancers. Currently, TTI-101 is under investigation in a Phase 1 single agent multicenter clinical trial in patients with advanced solid tumors. For more information about this ongoing trial of TTI-101, please visit ClinicalTrials.gov (NCT03195699).

Chronic Inflammation and Fibrosis

The pro-proliferative and pro-survival activity of STAT3 is also a central mediator for chronic inflammation and fibrosis. For example, a single allelic knockout of STAT3 inhibits fibrotic phenotypes in multiple murine models of fibrosis.

Tvardi’s second generation molecules target clinical indications for fibrotic diseases. STAT3 inhibition with Tvardi’s compounds has demonstrated reversal of fibrosis and restoration of normal function in models of idiopathic pulmonary fibrosis, non-alcoholic steatohepatitis and scleroderma.

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