Core Insights - Tvardi Therapeutics, Inc. has reported positive preliminary results from its Phase 2 REVERT IPF clinical trial of TTI-101, showing a 9.4% decrease in fibrosis score at week 12 compared to a 2.4% decrease in the placebo group [1][6] - The company is also progressing with its next-generation STAT3 inhibitor, TTI-109, with topline data expected in H1 2026 [1][5] Group 1: Clinical Trial Results - In the REVERT IPF trial, TTI-101 demonstrated a significant reduction in fibrosis scores, with a baseline-weighted high-resolution CT lung fibrosis score showing a decline of 9.4% for TTI-101 versus 2.4% for placebo [6] - A greater decline in IL-6 levels was observed in patients treated with TTI-101, indicating effective STAT3 pathway inhibition [6] - 63% of patients treated with TTI-101 showed an increase in FVC at 12 weeks, compared to 46% in the placebo group, with mean FVC change being -15mL for TTI-101 versus -22mL for placebo [6] Group 2: Company Strategy and Future Directions - The CEO of Tvardi highlighted the encouraging results from the REVERT IPF trial and expressed eagerness for the upcoming results from the TTI-109 study, which aims to enhance the efficacy and tolerability of STAT3 targeting [4][5] - The REVERT IPF trial was a randomized, double-blind, placebo-controlled study designed to assess safety and exploratory outcomes related to lung function, although it did not meet its initial goals based on preliminary data [5]

Summary of Trevi Therapeutics (TRVI) Conference Call Company Overview - **Company Name**: Trevi Therapeutics (TRVI) - **Founded**: 2018 - **Focus**: Development of small molecule therapeutics targeting STAT3, a transcription factor associated with proliferative diseases and fibrosis [4][5] Financial Highlights - **Initial Funding**: Raised approximately $9.5 million in 2018 - **Series B Funding**: Raised $74 million - **Recent Financing**: Reverse merged in April 2025, raising about $50 million, providing a cash runway into Q4 2026 [5][6][78] Clinical Development - **Lead Program**: Focused on idiopathic pulmonary fibrosis (IPF) with a double-blind randomized placebo-controlled trial set to unblind in Q4 2025 [5][6] - **Oncology Trials**: Data from oncology trials showed promising pharmacokinetics (PK) and pharmacodynamics (PD) with a significant reduction in activated STAT3 [20][27] - **Next Steps**: Anticipated data readouts for both IPF and hepatocellular carcinoma (HCC) in the first half of 2026 [78][80] Mechanism of Action - **STAT3 Inhibition**: Trevi's approach involves non-covalently binding to STAT3 to inhibit its activation without affecting the protein itself, avoiding mitochondrial toxicity seen in other inhibitors [9][10] - **Importance in IPF**: STAT3 is a central mechanism in fibrosis, with high expression correlating with increased mortality in patients [13][14] Competitive Landscape - **Recent Developments**: Notable successes in the IPF space from Boehringer Ingelheim and United Therapeutics, indicating a renewed interest in the market [15][18] - **Positioning**: Trevi's STAT3 inhibitors are seen as potentially disease-modifying, with mechanisms that could complement existing therapies [18][39] Trial Design and Data - **Interim Analysis**: Conducted to assess safety and efficacy, leading to the discontinuation of the 1200 mg dose due to adverse events [35][36] - **Patient Outcomes**: Over a third of patients showed improvement in forced vital capacity (FVC), indicating potential efficacy [38] Future Directions - **Next Generation Molecule**: Development of a prodrug (TTI-109) with improved bioavailability and reduced gastrointestinal side effects, expected to enter trials if current studies yield positive results [61][68] - **Funding Strategy**: Plans to raise additional funds based on positive data from ongoing trials to support further development [78][80] Key Takeaways - Trevi Therapeutics is positioned in a promising area of drug development targeting STAT3 for fibrotic diseases, with significant upcoming data readouts that could impact its market position and funding opportunities [39][80]