Tvardi Therapeutics Inc. (NASDAQ: TVRD) published preclinical data on Tuesday demonstrating that its oral STAT3 inhibitors showed biological activity in a mouse model of colitis-associated colorectal cancer.
The findings, posted in the International Journal of Molecular Sciences under the title "Colitis-Associated Colorectal Cancer—STAT3 Inhibition as a Preventive Strategy," found that TTI-101, the company's first-generation STAT3 inhibitor, accumulated in the colon at concentrations roughly eight times higher than in plasma.
In the azoxymethane-dextran sodium sulfate mouse model — designed to replicate the progression from chronic colitis to colorectal cancer — TTI-101 prevented the formation of colon polyps and adenocarcinomas, normalized STAT3-regulated colonic gene expression, and modulated proliferative programs linked to disease progression.
The new data marks the fourth preclinical colitis model in which Tvardi's STAT3 inhibitors have shown biological activity; prior studies employed three acute models representing different immune axes.
On the clinical side, TTI-109, a next-generation prodrug of TTI-101, has completed a Phase 1 healthy-volunteer study. The company plans to initiate clinical trials in gastrointestinal diseases once it receives IND clearance and additional funding becomes available.
Separately, TTI-101 is currently being evaluated in a Phase 1b/2 trial in patients with hepatocellular carcinoma.
Tvardi, based in Houston, describes itself as a clinical-stage biopharmaceutical company focused on developing oral small-molecule therapies targeting STAT3 to treat inflammatory and proliferative diseases.
