Tvardi's TTI-109 Phase 1 study confirms prodrug design and STAT3 target engagement

Tvardi Therapeutics, Inc. announced on July 7, 2026 topline Phase 1 results for TTI-109, described as a phosphate prodrug of TTI-101 designed to improve delivery and tolerability while preserving the parent compound's mechanism of action.¹

The study, conducted in three parts, included a randomized, double-blind, placebo-controlled single ascending dose study of TTI-109 at four doses (n=8/cohort)¹, a bioequivalence crossover comparing TTI-101 and TTI-109 in both sequences with a 48-hour washout (n=6/sequence)¹, and a randomized, double-blind, placebo-controlled multiple ascending dose study with 21 days of twice-daily dosing at four doses, plus a TTI-101 reference arm (n=8/cohort).¹

Key findings showed TTI-109 rapidly converted to TTI-101 within two hours and produced nearly identical plasma levels at molar-equivalent doses¹, with 21-day repeat dosing showing stable, dose-proportional pharmacokinetics, with TTI-101 concentrations above the STAT3 IC₅₀.¹ Pharmacodynamic data showed reductions of up to 60% across disease-relevant STAT3-driven immune cell populations including Th17 cells, Tfh and B cell subsets.¹

On tolerability, compared with TTI-101 at near-equivalent doses, diarrhea events with TTI-109 were substantially shorter in duration (0.46 vs. 3.35 days).¹

The company said it has identified dermatologic and gastrointestinal therapeutic areas with shared STAT3-driven disease biology, and that its ability to initiate these programs is subject to clearance of an Investigational New Drug application (IND) and the availability of additional funding.¹ Tvardi is separately conducting a Phase 1b/2 clinical trial of TTI-101 in hepatocellular carcinoma (NCT05440708).¹