TTI-109

August 19, 2026: Tvardi Therapeutics presented a webinar on TTI-109, an oral prodrug of TTI-101, for ulcerative colitis (UC), outlining rationale, Phase 1 findings, and a proposed proof-of-concept trial. TTI-109 was described as showing rapid conversion with dose-proportional exposure above the STAT3 IC50, GI tolerability similar to placebo and improved versus TTI-101, and immune modulation in healthy volunteers.

In a Phase 1 multiple ascending dose cohort, TTI-109 reduced STAT3-driven immune populations, with placebo-adjusted declines including Th17 cells (-54%), T follicular helper cells (-34%), B cells (-20%), memory B cells (-46%), class-switched memory (-56%), switched memory IgG+ (-71%), and switched memory IgA+ (-42%). The company also cited TTI-101 clinical and preclinical support, including reduced pY-STAT3, IL-6, and fibrosis; in pooled IPF Phase 2 data, fibrosis score changed -9.4% for TTI-101 vs -2.4% for placebo, and IL-6 decline showed a 4.5-fold difference in slope.

Tvardi proposed a randomized UC induction/maintenance study in moderate-to-severe, advanced-therapy-experienced patients, with a 12-week induction and 12-week maintenance period; primary endpoint is safety and secondary endpoint includes clinical remission at 12 weeks.

Upcoming catalysts: TTI-109 IND submission expected in 2027 and UC study initiation expected in 2027, subject to IND clearance and funding; TTI-101 Phase 1b/2 topline data in hepatocellular carcinoma are expected in 4Q 2026.