Abiopharma

TVARDI THERAPEUTICS, INC. (TVRD) Announces Clinical Trial Update TVARDI THERAPEUTICS, INC. (TVRD) provided an update on its clinical development programs. Clinical Development Highlights:

• Drug Program: indication, implicated
• Diseases/Conditions: ulcerative colitis (UC), its next generation STAT3 inhibitor
• Clinical Stage: Phase 1
• Update Type: Trial Timeline Adjustment
• Primary Factors: Regulatory Process
• Collaboration: STAT3
  • targeting STAT3 to treat inflammatory and proliferative diseases, today announced that it has selected ulcerative colitis (UC) as the initial disease indication for its next generation STAT3 inhibitor, TTI-109. Tvardi’s decision follows its successful Phase 1 healthy volunteer study, in which TTI-109 successfully modulated multiple STAT3-driven immune cell populations, including Th17, T follicular helper (Tfh) and B cells. These same cell types are known to expand with UC disease severity and infiltrate the inflamed colon. Further analysis of immune cell populations across the active dose range elucidated: ·Broad suppression of pathogenic Th17-associated immune populations, including up to 76% reduction in subsets associated with mucosal destruction and treatment-refractory UC ·The Tfh immune populations that drive mucosal B cell responses were reduced up to 43% in Tfh subsets associated with disease UC activity ·Suppression extended to B cell (humoral) immunity, including up to 71% decline in subsets associated with colonic inflammation STAT3 sits at the center of the three interconnected processes that drive UC: immune dysregulation, chronic inflammation and the tissue remodeling that leads to fibrosis, positioning it as a single, convergent therapeutic target for a disease with multiple underlying drivers. These findings are further supported by published clinical studies linking reductions in activated STAT3 with higher rates of clinical remission across multiple UC therapeutic classes. UC is a large and underserved market. More than 1.25 million patients are diagnosed with UC in the United States, representing an addressable market of approximately $3 billion in the U.S. and $9 billion globally. Currently approved therapies, including anti-TNF, anti-integrin, anti-IL-12/23, S1P and JAK inhibitors, achieve placebo-adjusted clinical remission rates below 30%, and most are administered parenterally. Additionally, JAK inhibitors carry a black box warning for major adverse cardiovascular events, mortality, thrombosis, serious infections and malignancy. By contrast, TTI-109, an oral small molecule, is designed to inhibit STAT3 directly, addressing the inflammation, immune dysregulation and proliferation that single-pathway therapies leave unresolved. Across more than 400 subjects dosed to date with Tvardi’s STAT3 inhibitors demonstrated a differentiated safety profile from JAK inhibitors. TTI-109 is administered orally without a loading dose, and in preclinical models of UC, achieved more than eight-fold greater drug concentration in target tissue relative to plasma. Imran Alibhai, Ph.D., Chief Executive Officer of Tvardi, stated, “In our healthy volunteer study we observed reductions across immune cell populations that the published literature implicates in UC pathogenesis, and we saw them consistently across the active dose range. STAT3 sits downstream of the cytokines that drive UC, including IL-23, IL-6 and IL-17. We believe a single oral agent acting at that convergence point has the potential to help patients who have not responded adequately to a biologic or JAK inhibitor. This is what led us to prioritize UC as our initial indication for TTI-109.” Planned UC Clinical Trial Tvardi plans to initiate a study of TTI-109 in patients with moderate-to-severe UC in 2027
  • targeting STAT3 to treat inflammatory and proliferative diseases with significant unmet need. STAT3 is a central mediator across critical signaling pathways that drive uncontrolled proliferation, survival and immune dysregulation. STAT3 is also positioned at the intersection of many signaling pathways integral to the survival and immune evasion of cancer cells. The Company has completed a Phase 1 healthy volunteer study of TTI-109 and plans to initiate a clinical trial of TTI-109 in its initial indication, ulcerative colitis, pending IND clearance and the availability of additional funding. The company is also conducting a Phase 1b/2 clinical trial of TTI-101 in hepatocellular carcinoma (NCT0544