TTI-109

July 7, 2026: Tvardi Therapeutics, Inc. (NASDAQ: TVRD) reported Phase 1 results for TTI-109, a phosphate prodrug of its STAT3 inhibitor TTI-101 designed to improve delivery and tolerability. In a three-part Phase 1 healthy volunteer program (single ascending dose; TTI-101 vs TTI-109 bioequivalence crossover; and 21-day multiple ascending dose with a TTI-101 reference arm), TTI-109 rapidly converted to TTI-101 within two hours and achieved nearly identical plasma exposures at molar-equivalent doses. With 21 days of twice-daily dosing, pharmacokinetics were stable and dose-proportional, with TTI-101 concentrations above the STAT3 IC50. Exploratory pharmacodynamics showed reductions of up to 60% in STAT3-driven immune cell populations (Th17, T follicular helper, and B-cell subsets). Safety/tolerability: diarrhea events were transient and resolved without treatment interruption; versus near-equivalent TTI-101 doses, diarrhea duration was shorter with TTI-109 (0.46 vs 3.35 days).

Tvardi plans to advance TTI-109 into STAT3-driven dermatologic and gastrointestinal diseases, contingent on IND clearance and additional funding. The company is also conducting a Phase 1b/2 trial of TTI-101 in hepatocellular carcinoma (NCT05440708). An investor webcast is scheduled for July 7, 2026 at 8:30 a.m. ET.