Tvardi Therapeutics (Nasdaq: TVRD) Soars on Positive Phase 1 Results for Next-Gen STAT3 Inhibitor TTI-109

Investorideas.com (www.investorideas.com) a trusted platform for investing ideas, including biotech and medical tech stocks, issues a news and trading alert for Tvardi Therapeutics, Inc. (NASDAQ: TVRD), a clinical-stage biopharmaceutical company focused on the development of novel, oral, small molecule therapies targeting STAT3 to treat inflammatory and proliferative diseases.

The stock makes the Nasdaq top gainers list on news, currently trading at 2.9700 +0.9600 (+47.76%) on volume of over 49 Million shares as of this report. The stock has day’s range of 2.0700 – 3.8599.

Tvardi Therapeutics today announced Phase 1 results for TTI-109, its next-generation STAT3 inhibitor. TTI-109 is a phosphate prodrug of TTI-101 designed to improve delivery and tolerability while preserving the parent compound’s mechanism of action. The study confirmed rapid prodrug conversion, dose-proportional pharmacokinetics with exposures above the STAT3 IC50 and, in an exploratory pharmacodynamic analysis, reductions of up to 60% in STAT3-driven immune cell populations across Th17, Tfh and B cell subsets.

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Key findings include:

• Confirmed prodrug conversion and exposure equivalence: Validating its prodrug design, TTI-109 rapidly converted to TTI-101 within two hours and produced nearly identical plasma levels at molar-equivalent doses.
• Sustained target-level exposure: 21-day repeat dosing showed stable, dose-proportional pharmacokinetics, with TTI-101 concentrations above the STAT3 IC50.
• Evidence of target engagement: Pharmacodynamic data showed reductions of up to 60% across disease-relevant STAT3-driven immune cell populations including Th17 cells, Tfh and B cell subsets.
• Improved tolerability vs. TTI-101: Compared with placebo, diarrhea events with TTI-109 were similar in duration, transient, and resolved without treatment interruption. Compared with TTI-101 at near-equivalent doses, diarrhea events with TTI-109 were substantially shorter in duration (0.46 vs. 3.35 days).

“These Phase 1 results validate our prodrug strategy on every objective we set out to test. TTI-109 matched TTI-101’s exposure at molar-equivalent doses with substantially better tolerability and delivered a pharmacodynamic signal across disease-relevant immune cell populations that we would not typically expect to see in healthy volunteers. That combination of findings supports our development pathway into Phase 2,” said Imran Alibhai, Ph.D., Chief Executive Officer of Tvardi.

The study was conducted in three parts. Part A was a randomized, double-blind, placebo-controlled single ascending dose study of TTI-109 at four doses (n=8/cohort). Part B was a bioequivalence crossover comparing TTI-101 and TTI-109 in both sequences with a 48-hour washout (n=6/sequence). Part C was a randomized, double-blind, placebo-controlled multiple ascending dose study with 21 days of twice-daily dosing at four doses, plus a TTI-101 reference arm (n=8/cohort).

Primary objectives were to confirm rapid conversion of TTI-109 to TTI-101, demonstrate equivalent exposures at molar-equivalent doses, demonstrate dose-dependent increases in TTI-101 exposure and characterize safety and tolerability versus TTI-101 and placebo. Pharmacodynamic effects were an exploratory objective.

Tvardi Plans to Advance TTI-109 Across Dermatologic and GI Therapeutic Areas

The Company has identified dermatologic and gastrointestinal therapeutic areas with shared STAT3-driven disease biology, specifically the convergence of cytokines, growth factors and Th17 and B cell immune pathways at the STAT3 node. TTI-109 is designed to address both the cellular and humoral components of inflammation and proliferation with a single oral agent. Recent programs in related STAT3-driven indications have validated the underlying biology, but each acts on a single upstream target, while TTI-109 targets STAT3, the downstream node where these pathways converge.

STAT3 sits at the center of the core disease processes in dermatologic and gastrointestinal diseases, including inflammation, proliferation and cellular and humoral dysregulation. Tvardi’s STAT3 inhibitors have demonstrated biologic activity in these pathways in both preclinical models and in the clinic. In preclinical disease models, the Company’s STAT3 inhibitors reduced inflammatory cascades, fibrosis and modulated immune activity. Similarly, in humans, TTI-101 reduced activated STAT3 levels, inflammatory cascades and fibrosis. The TTI-109 healthy volunteer study extended this translational profile, with reductions in STAT3-driven immune cell populations.

“The diseases we are targeting are still largely managed with parenteral therapies that each block a single pathway,” said Dr. Alibhai. “Because STAT3 sits downstream of multiple convergent signals, a single oral STAT3 inhibitor has the potential to do what no single-pathway biologic can and we believe our preclinical, clinical and now pharmacodynamic data are building a consistent case that TTI-109 is a promising molecule to test this hypothesis.”

Tvardi’s ability to initiate these programs is subject to clearance of an Investigational New Drug application (IND) and the availability of additional funding.