Core Insights - Trevi Therapeutics presented additional analyses from the Phase 2a RIVER trial of Haduvio, which showed a statistically significant reduction in 24-hour cough frequency of 67% from baseline and 57% on a placebo-adjusted basis (p<0.0001) for patients with refractory chronic cough (RCC) [1][2] Company Overview - Trevi Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on developing Haduvio™ (oral nalbuphine ER) for chronic cough treatment in patients with idiopathic pulmonary fibrosis (IPF) and RCC [7] - Haduvio is the first investigational therapy to demonstrate a statistically significant reduction in cough frequency in clinical trials for both IPF and RCC patients [7] Phase 2a RIVER Trial Details - The Phase 2a RIVER trial was a randomized, double-blind, placebo-controlled study with two treatment periods, each lasting 21 days, separated by a 21-day washout period [5] - The primary endpoint was the mean change in 24-hour cough frequency, assessed by an objective cough monitor at Day 21 [5] Refractory Chronic Cough (RCC) Insights - RCC affects approximately 2-3 million patients in the U.S. and is characterized by a persistent cough lasting over 8 weeks despite treatment for underlying conditions [6] - There are currently no approved therapies for RCC in the U.S., making Haduvio a potentially significant treatment option [6] Efficacy and Safety Findings - Responder analyses indicated statistically significant reductions in 24-hour cough frequency at thresholds of 30%, 50%, and 75% for patients on Haduvio across all doses [8] - Patients reported significant improvement in the Leicester Cough Questionnaire at Day 21 for the 108 mg BID dose (p<0.0001) [8] - Adverse events were more frequently observed during the initial exposure to Haduvio, particularly at the 27 mg BID dose, but diminished over time [8]

Financial Data and Key Metrics Changes - For Q4 2024, the company reported a net loss of $11.4 million, compared to a net loss of $7.8 million in Q4 2023, indicating a deterioration in financial performance [17] - R&D expenses increased to $9.3 million in Q4 2024 from $6.5 million in Q4 2023, primarily due to higher clinical trial costs [17] - G&A expenses rose to $2.9 million in Q4 2024 from $2.4 million in Q4 2023, mainly due to increased stock-based compensation and personnel-related expenses [17] - As of December 31, 2024, cash, cash equivalents, and marketable securities totaled $107.6 million, bolstered by a $50 million offering completed in December [18] Business Line Data and Key Metrics Changes - The company achieved three positive data readouts in 2024, including studies related to chronic cough patients with IPF and refractory chronic cough [3][4] - The Human Abuse Potential Study showed statistically significant lower drug liking compared to butorphanol, supporting the drug's profile [6] - The Sample Size Re Estimation analysis confirmed the original sample size of 160 patients for the Phase 2b study in IPF chronic cough, allowing the company to stay on track for enrollment [8] Market Data and Key Metrics Changes - The RIVER trial in patients with refractory chronic cough showed a 57% placebo-adjusted change from baseline with a p-value of less than 0.0001, indicating strong efficacy [11] - The company is targeting a subsegment of the refractory chronic cough population, focusing on patients who have failed prior therapies, which represents a significant unmet need [12] Company Strategy and Development Direction - The company plans to develop HEDUVO in serious chronic cough conditions, positioning it as a first-in-class therapy in IPF and potentially best-in-class across chronic cough indications [15] - The next steps include preparing for an end-of-Phase 2 meeting with the FDA for the IPF program and developing a protocol for the next RCC study [13] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the execution of clinical trials and the positive data readouts, which are expected to drive future growth [3][4] - The company anticipates cash burn of approximately $12 million to $14 million per quarter in Q1 and Q2 of 2025, with guidance remaining unchanged for cash runway into the second half of 2026 [18][19] Other Important Information - The company plans to present more data at upcoming conferences, including the American Thoracic Society meeting in May and the European Respiratory Society Congress in September [14][15] - The company is actively planning for the next steps in the development of HEDUVO, with a focus on both IPF and RCC [12] Q&A Session Summary Question: Could you speak about the patients enrolled in the CORAL study? - Management confirmed that no changes were made to the study protocol or sites after the sample size estimation, maintaining consistency in the patient population [22][23] Question: Can you comment on the discontinuation rate in the CORAL study? - The discontinuation rate remained in single digits throughout the study, indicating stability in patient retention [24] Question: What are the placebo response expectations for the IPF chronic cough Phase 2 study? - Management indicated that the placebo effect has been well-behaved in prior studies, with conservative assumptions around the expected effect size [29] Question: How will the RCC patient population be split between P2X3 and HEDUVO? - The company plans to target treatment failure patients, suggesting that HEDUVO will be considered after P2X3 therapy fails [33] Question: What secondary endpoints will matter most for driving HEDUVO prescriptions? - Management highlighted the importance of linking secondary endpoints to the primary endpoint of objective cough severity, with quality of life metrics also being considered [80]