Tvardi Therapeutics (TVRD) Study result summary

Study design and objectives

• Phase I healthy volunteer study evaluated TTI-109, a phosphate prodrug of TTI-101, across single and multiple ascending dose cohorts, including a bioequivalence crossover with TTI-101, focusing on pharmacokinetics, safety, tolerability, and pharmacodynamics.

• Primary objectives included confirming rapid prodrug conversion, exposure equivalence, dose-dependent pharmacokinetics, and safety/tolerability versus TTI-101 and placebo.

• Exploratory pharmacodynamic effects were also assessed.

Key pharmacokinetic and pharmacodynamic findings

• TTI-109 demonstrated rapid and predictable conversion to TTI-101 in humans, with >95% conversion within two hours and nearly identical plasma levels at molar-equivalent doses.

• Dose-proportional pharmacokinetics were observed, with exposures above the STAT3 IC50 at all active doses and stable concentrations over 21 days.

• Equivalent exposures were confirmed between TTI-109 and TTI-101 at equal molar dosing.

• Pharmacodynamic analysis revealed up to 60% reductions in STAT3-driven immune cell populations, including Th17, T follicular helper, and B cell subsets, as well as 16 immune subsets linked to inflammatory and proliferative diseases.

Safety and tolerability

• TTI-109 exhibited a favorable safety profile, with TEAE rates similar to placebo and improved GI tolerability compared to TTI-101.

• Diarrhea incidence and duration with TTI-109 were comparable to placebo and less than with TTI-101 (0.46 vs. 3.35 days).

• No serious adverse events, dose-dependent adverse event patterns, or clinically relevant changes in vital signs or ECGs were observed.

• One case of transaminitis was deemed unlikely related to TTI-109, with no evidence of DILI.