Tvardi Therapeutics (TVRD) investor relations material

Program overview

• STAT3-focused portfolio spans oncology and inflammatory disease; phase I solid-tumor data showed PK/PD activity and tolerability, with a liver cancer phase II readout expected later in 2026.

• TTI-109 is expected to advance in I&I, while TTI-101 remains the oncology molecule.

IPF findings and formulation

• The U.S. IPF trial did not meet its goals; discontinuations were higher than expected when TTI-101 was combined with background nintedanib, which most participants received.

• In completers, TTI-101 showed a greater than fourfold decrease in IL6 versus placebo and a 7% placebo-adjusted decline in fibrosis after 12 weeks; FVC results were confounded by no decline in the placebo arm.

• TTI-109, an inert prodrug that converts to active drug systemically, showed placebo-like GI tolerability in phase I and reduced UC-associated T-cell and B-cell populations in healthy volunteers.

Mechanism and safety

• The non-covalent approach inhibits STAT3 activation without removing the protein; management contrasted this with covalent inhibitors linked to mitochondrial toxicities.

• Across 400 subjects treated with TTI-101 and TTI-109, no drug-related mitochondrial toxicity was observed.

• Preclinical models, nine-month monkey toxicology, and patient treatment up to two years showed no reported wound-healing issues; long-term mouse data indicated changes in gut dysbiosis and the microbiome.