Tvardi's TTI-109 Shows Improved Tolerability And Target Engagement In Phase 1 Study
(RTTNews) - Tvardi Therapeutics, Inc. (TVRD) has reported results from its Phase 1 study of TTI-109, its next-generation STAT3 inhibitor, confirming the drug's prodrug design and improved tolerability compared to its predecessor TTI-101.
The study was conducted in three parts. TTI-109, a phosphate prodrug of TTI-101, was rapidly converted in the body within two hours, achieving plasma levels nearly identical to TTI-101 at equivalent doses. The study demonstrated sustained exposure above the STAT3 inhibitory threshold during 21 days of repeat dosing, validating its pharmacokinetic profile.
Importantly, exploratory pharmacodynamic analyses showed reductions of up to 60% in STAT3-driven immune cell populations, including Th17, T follicular helper (Tfh), and B cell subsets.
Tolerability was a key highlight. Compared with TTI-101, diarrhoea events linked to substantially shorter in duration (0.46 vs. 3.35 days). TTI-109 were substantially shorter in duration (0.46 vs. 3.35 days), and episodes were transient, resolving without treatment interruption.
Imran Alibhai, Ph.D., Chief Executive Officer of Tvardi, stated that the results "validate our prodrug strategy on every objective we set out to test," noting that the combination of exposure equivalence, improved tolerability, and pharmacodynamic signals supports advancement into Phase 2.
The company plans to move TTI-109 into Phase 2 studies targeting STAT3-driven dermatologic and gastrointestinal diseases, contingent on additional funding.
TVRD has traded between $1.50 and $43.65 over the past year. The stock closed Monday's trading at $2.01, down 0.50%. In pre-market trading the stock is at $2.05, up 1.99%.
