Tvardi Therapeutics (TVRD) investor relations material

Company overview and scientific focus

• Focuses on STAT3, a key transcription factor involved in inflammatory and proliferative disorders, with broad implications for oncology and immune diseases.

• Developed an orally delivered small molecule STAT3 inhibitor, tested in nearly 400 patients to date.

• STAT3 inhibition is positioned as a potential node to address redundancy in multiple signaling pathways.

Clinical trial insights and challenges

• Initial TTI-101 program targeted both oncology and pulmonary fibrosis, with proof-of-mechanism in the latter.

• REVERT-IPF trial faced confounding factors: unexpectedly low placebo decline in lung function and high discontinuation rates due to GI events, especially with nintedanib background therapy.

• Post hoc analysis of completers showed a 7% placebo-adjusted reduction in fibrosis, a novel finding in the field, supported by blinded HRCT and IL-6 biomarker data.

• The trial's limitations highlighted the need for longer studies and careful management of background therapies.

Next-generation molecule and development strategy

• TTI-109, a prodrug of TTI-101, was designed for improved oral delivery and reduced GI exposure, potentially mitigating prior tolerability issues.

• Preclinical studies showed rapid conversion of TTI-109 to active TTI-101 in animals, with similar pharmacokinetics expected in humans.

• Phase I healthy volunteer study includes single and multiple ascending dose arms, bioequivalence, and pharmacodynamic assessments, with data expected in June.

• Immune cell profiling and inflammatory markers are being evaluated as pharmacodynamic endpoints.