Tvardi is focused on the development of novel, oral small molecule therapies targeting STAT3 to treat inflammatory and proliferative diseases with significant unmet need. Based upon Tvardi’s founders’ seminal work and deep understanding of the transcription factor STAT3, the company has designed an innovative approach to directly inhibit STAT3, a highly validated, yet historically undruggable target. Leveraging this expertise, the company is developing a pipeline of STAT3 inhibitors with a differentiated mechanism of action and convenient oral dosing.

Tvardi’s pipeline includes two oral, small molecule STAT3 inhibitors: TTI-101 and TTI-109. TTI-101 is Tvardi’s first-generation direct STAT3 inhibitor, currently in a Phase 2 clinical trial in hepatocellular carcinoma (NCT05440708). TTI-109 is a phosphate prodrug of TTI-101 that is mechanistically identical to its parent molecule but is designed to enhance the company’s ability to target STAT3. Tvardi recently completed a clinical trial with TTI-109 in healthy volunteers. The study confirmed rapid prodrug conversion, dose-proportional pharmacokinetics with exposures above the STAT3 IC50 and reductions of up to 60% in STAT3-driven immune cell populations across Th17, Th and B cell subsets.

Tvardi believes their approach to directly inhibiting STAT3 enables them to develop product candidates with the potential to provide meaningful therapeutic benefit to patients with inflammatory and proliferative diseases.