Tvardi Therapeutics (TVRD) Corporate presentation summary

Scientific rationale and mechanism of action

• STAT3 is a central mediator in inflammatory and proliferative diseases, integrating multiple upstream signals and driving immune dysregulation, inflammation, and proliferation.

• Inhibiting STAT3 nuclear function blocks disease drivers without affecting mitochondrial function, offering a targeted approach.

• TTI-109 is an oral prodrug rapidly converted to active TTI-101, designed to enhance delivery, improve GI tolerability, and maintain clinical activity.

• Preclinical and clinical studies confirm reduction in pY-STAT3, immune cell dysregulation, inflammation, and proliferation.

• TTI-109 modulates both cellular (Th17, Tfh) and humoral (B cell) immune populations implicated in ulcerative colitis (UC) pathology.

Clinical development and safety profile

• Phase 1 studies validated rapid conversion of TTI-109 to TTI-101, with dose-proportional pharmacokinetics and exposures above STAT3 IC50.

• TTI-109 demonstrated a safety profile similar to placebo and improved over TTI-101, with most adverse events being mild and transient.

• Diarrhea incidence and duration with TTI-109 were comparable to placebo and shorter than with TTI-101.

• No serious adverse events or dose-dependent safety signals were observed.

• TTI-109 achieved equivalent active moiety exposure to TTI-101 in bioequivalence studies.

Efficacy and immune modulation in UC and other indications

• TTI-109 downregulated key STAT3-driven immune populations (Th17, Tfh, B cells) by up to 60% in healthy volunteers.

• Broad suppression of pathogenic Th17, Tfh, and B cell subsets was observed, supporting the rationale for UC treatment.

• Preclinical and clinical data show reduction in IL-6, fibrosis, and improvement in tissue integrity in models of UC and IPF.

• TTI-101 and TTI-109 normalized immune cell populations and reduced inflammation and fibrosis in both animal models and patients.

• Clinical proof-of-concept in oncology and IPF demonstrated target engagement and biological activity.