STAT3 Inhibitor Blocks Colon Tumors
Tvardi Therapeutics STAT3 Inhibitor Prevents Colon Tumors in Preclinical Mouse Models
Anonymous
Tvardi Therapeutics reported that its first-generation STAT3 inhibitor, TTI-101, reached pharmacologically relevant concentrations in the colon in a mouse model of chronic colitis and prevented colon polyps and adenocarcinomas while altering STAT3-linked gene activity. The findings add to results across several preclinical colitis models and support further investigation of STAT3 inhibition for ulcerative colitis, but they do not establish benefit in people. Tvardi says the research supports the rationale for its next-generation candidate, TTI-109; gastrointestinal trials of TTI-109 remain contingent on regulatory clearance and additional funding.
Key Points
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The study’s AOM-DSS mouse model was designed to mimic the progression from chronic colitis to colorectal cancer; the articles note that people with ulcerative colitis are estimated to face a 20- to 30-fold higher CRC risk than the general population.
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TTI-101 reached approximately eight times higher concentrations in the colon than in plasma, indicating accumulation in the target organ at levels the company described as pharmacologically relevant for inhibiting STAT3-dependent proliferation.
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Tvardi said this chronic AOM-DSS study was the fourth preclinical colitis model showing biological activity. Earlier studies involved DSS, TNBS and oxazolone models, representing distinct immune pathways—innate/Th17, adaptive Th1, and adaptive Th2/NKT, respectively.
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