Company Overview - Trevi Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on developing Haduvio™ (oral nalbuphine ER) for treating chronic cough in patients with idiopathic pulmonary fibrosis (IPF) and refractory chronic cough (RCC) [5] - Haduvio acts on the cough reflex arc as a kappa agonist and mu antagonist (KAMA), targeting opioid receptors involved in controlling chronic cough [5] Public Offering Details - Trevi Therapeutics has initiated an underwritten public offering of $100,000,000 of its common stock, with an additional option for underwriters to purchase up to $15,000,000 more [1] - The offering is being managed by Morgan Stanley, Leerink Partners, Stifel, and Cantor as joint book-running managers [2] - The shares are offered under a shelf registration statement filed with the SEC, which was declared effective on August 15, 2023 [3] Offering Conditions - The completion of the offering is subject to market and other conditions, with no assurance on the timing or terms of the offering [2] - A preliminary prospectus supplement detailing the terms of the offering is expected to be filed with the SEC [3]

Core Insights - Trevi Therapeutics, Inc. reported positive topline results from its Phase 2b CORAL trial of Haduvio for chronic cough in patients with idiopathic pulmonary fibrosis (IPF), achieving the primary endpoint with statistically significant reductions in 24-hour cough frequency across all dose groups at week six [1][2]. Group 1: Trial Results - The 108 mg BID, 54 mg BID, and 27 mg BID dose groups achieved reductions from baseline of 60.2%, 53.4%, and 47.9%, respectively, compared to a placebo reduction of 16.9% [2]. - A rapid reduction in 24-hour cough frequency was observed at week two, with 65% of patients on 108 mg BID, 63% on 54 mg BID, and 60% on 27 mg BID experiencing a 50% reduction at week six, compared to 19% of placebo patients [5]. - Statistically significant improvements were noted in secondary endpoints for the 108 mg BID and 54 mg BID dose groups, including a mean reduction of 3.0 points for 108 mg BID and 3.2 points for 54 mg BID on the cough-severity numerical rating scale, compared to a 1.5-point reduction for placebo [5]. Group 2: Safety and Discontinuation - Discontinuation rates due to adverse events were similar between the Haduvio (5.6%) and placebo groups (5%) [4]. Group 3: Stock Performance - Following the announcement, Trevi Therapeutics' stock declined by 10.45%, trading at $5.83 [4].

Summary of Trevi Therapeutics Inc (TRVI) Update - June 02, 2025 Company Overview - **Company**: Trevi Therapeutics Inc (TRVI) - **Focus**: Development of Haduvio for the treatment of chronic cough in patients with idiopathic pulmonary fibrosis (IPF) Key Industry Insights - **Chronic Cough in IPF**: - Approximately 140,000 patients with IPF in the U.S. - Up to 85% of IPF patients report chronic cough, significantly impacting their quality of life [8][9] - No FDA-approved therapies for chronic cough in IPF patients [9][34] Core Findings from the CORAL Phase IIb Trial - **Trial Results**: - First positive results in a Phase IIb trial for chronic cough in IPF patients [10] - Dose-related response observed: - 60% reduction in cough frequency at the highest dose (108 mg BID) - 48% reduction at the lowest dose (27 mg BID) - Placebo-adjusted difference of 43% at the highest dose [11][21] - Majority of patients (approximately 60-65%) achieved a 50% or greater reduction in cough frequency [23] - Rapid onset of effect observed as early as week two [12][22] - **Patient Reported Outcomes**: - Significant improvements in cough frequency and severity reported by patients [24][26] - At week six, the 54 mg and 108 mg BID groups showed significant differences from placebo [25] - **Safety Profile**: - Low discontinuation rates: 5% for placebo and 5.6% for Haduvio [12][27] - Common adverse events included nausea, vomiting, and headache, consistent with previous studies [28] Future Development Plans - **Phase III Program**: - Plans to request an end of Phase II meeting with the FDA to align on the Phase III program for IPF chronic cough [35] - Anticipated initiation of a trial for chronic cough in non-IPF interstitial lung disease (ILD) by the end of 2025 [33] - **Market Opportunity**: - High unmet need in both IPF and non-IPF ILD chronic cough, with potential to double the market size [33][34] - Expected rapid uptake in physician prescribing due to lack of effective therapies [30] Competitive Landscape - **Positioning**: - Trevi aims to be best-in-class and first-in-class for chronic cough treatment in IPF [30] - Current off-label treatments are ineffective, highlighting the commercial opportunity for Haduvio [32] Additional Considerations - **Patient Impact**: - Chronic cough significantly affects patients' quality of life, leading to social isolation and reduced activity levels [42][43] - Immediate benefits of Haduvio could lead to high patient adherence [46][70] - **Regulatory and Research Considerations**: - Ongoing discussions with the FDA regarding study design and duration for Phase III trials [52][53] - Future data on patient-reported outcomes and safety will inform dosing strategies [97][108] This summary encapsulates the key points from the Trevi Therapeutics conference call, focusing on the company's advancements in treating chronic cough associated with IPF and the implications for future research and market positioning.

Controlling cough where it countsTM Positive Topline Results from Phase 2b Trial of Haduvio in Patients with IPF Chronic Cough (CORAL) June 2, 2025 Nasdaq: TRVI Forward Looking Statement Disclaimer Statements contained in this presentation and oral statements made regarding the subject of this presentation regarding matters that are not historical facts are "forward- looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Such statements are subject to risks and uncer ...

Core Insights - Trevi Therapeutics announced positive topline results from its Phase 2b CORAL trial for Haduvio, demonstrating significant reductions in 24-hour cough frequency in patients with idiopathic pulmonary fibrosis (IPF) [1][2][9] Trial Results - The primary endpoint was achieved with Haduvio showing statistically significant reductions in cough frequency: 60.2% for 108 mg BID, 53.4% for 54 mg BID, and 47.9% for 27 mg BID, compared to a 16.9% reduction in the placebo group [1][3][9] - A rapid reduction in cough frequency was observed at Week 2, with 65% of patients on 108 mg BID achieving a 50% reduction by Week 6 [11] - Discontinuation rates due to adverse events were similar between Haduvio (5.6%) and placebo (5.0%) groups, indicating a favorable safety profile [6][9] Future Plans - Trevi plans to request an End-of-Phase 2 meeting with the FDA and initiate the Phase 3 program in the first half of 2026 [1][7] - The CORAL trial is a significant milestone as it is the first positive Phase 2b study for chronic cough in IPF patients, addressing an unmet medical need [2][9] Background on IPF and Chronic Cough - Chronic cough affects approximately 85% of IPF patients, with around 140,000 patients in the U.S. suffering from IPF [10][12] - There are currently no approved therapies for chronic cough in this population, highlighting the importance of Haduvio's development [12][13]

Core Insights - Trevi Therapeutics, Inc. is set to announce topline results from the Phase 2b CORAL trial of its investigational therapy Haduvio for chronic cough in patients with idiopathic pulmonary fibrosis (IPF) during a conference call on June 2, 2025 [1][2] Company Overview - Trevi Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on developing Haduvio (oral nalbuphine extended-release) for chronic cough treatment in patients with IPF and refractory chronic cough (RCC) [4] - Haduvio is the first investigational therapy to demonstrate a statistically significant reduction in cough frequency in clinical trials for both IPF chronic cough and RCC [4] - The mechanism of Haduvio involves acting on the cough reflex arc as a kappa agonist and mu antagonist, targeting opioid receptors crucial for cough control [4] Industry Context - Chronic cough affects up to 85% of the IPF population, with approximately 140,000 patients in the U.S. suffering from IPF [3] - Patients with chronic cough may experience up to 1,500 coughs per day, leading to significant declines in their quality of life and increased risks of disease progression, death, or lung transplant [3] - Currently, there are no approved therapies for chronic cough in IPF patients, and existing off-label treatments offer minimal benefits [3]

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 refractory chronic cough (RCC) [3][4] - Haduvio is the first investigational therapy to demonstrate a statistically significant reduction in cough frequency in clinical trials involving IPF and RCC patients [3][4] Industry Context - Chronic cough affects up to 85% of the IPF population, with approximately 150,000 IPF patients in the U.S. experiencing severe coughing, up to 1,500 times per day [4] - There are currently no approved therapies for chronic cough in IPF patients, and existing off-label treatments offer minimal benefits [4] - Refractory chronic cough, affecting around 2-3 million patients in the U.S., is characterized by a persistent cough lasting over 8 weeks despite treatment for underlying conditions, and it has no approved therapies [5] Upcoming Conferences - Trevi management will participate in several conferences in June 2025, including: - American Cough Conference on June 6-7, with an oral presentation on the RIVER trial [2] - CPDD 87th Annual Scientific Meeting on June 14-18, featuring a poster on the human abuse potential of nalbuphine [2] - BIO International Convention on June 16-19, with a corporate presentation scheduled for June 17 [3]

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]

Group 1 - Trevi Therapeutics, Inc. (TRVI) shares have increased by 4.1% over the past four weeks, closing at $6.46, with a mean price target of $19.06 indicating a potential upside of 195.1% [1] - The average of eight short-term price targets ranges from a low of $11 to a high of $29, with a standard deviation of $6.01, suggesting a potential increase of 70.3% to 348.9% from the current price level [2] - Analysts show strong agreement regarding TRVI's ability to report better earnings than previously predicted, which supports the view of potential upside [4][11] Group 2 - The Zacks Consensus Estimate for TRVI's current year has increased by 21.5% over the past month, with five estimates rising and no negative revisions [12] - TRVI holds a Zacks Rank 2 (Buy), placing it in the top 20% of over 4,000 ranked stocks based on earnings estimates, indicating a strong potential upside [13] - While consensus price targets may not be reliable for predicting exact gains, they can provide a directional guide for price movement [10][13]

Financial Data and Key Metrics Changes - For Q1 2025, the company reported a net loss of $10.4 million, an improvement from a net loss of $10.9 million in Q1 2024 [14] - R&D expenses decreased to $7.8 million in Q1 2025 from $8.8 million in Q1 2024, primarily due to reduced costs related to a human abuse potential study [14] - G&A expenses increased to $3.7 million in Q1 2025 from $3.1 million in Q1 2024, mainly due to higher personnel-related expenses [15] - As of March 31, 2025, cash and investments totaled $103.3 million, providing a runway into Q4 2026 [15] Business Line Data and Key Metrics Changes - The Phase 2a RIVER trial in RCC patients showed a 57% placebo-adjusted reduction in cough frequency, achieving a p-value of less than 0.0001 [7][8] - The Phase 2b CORAL trial for IPF chronic cough patients completed enrollment with approximately 160 patients across 10 countries [9] Market Data and Key Metrics Changes - RCC affects approximately 2 to 3 million patients in the U.S. with no approved therapies currently available [5] - The company is preparing for data release from the CORAL trial, which is expected to provide insights into treatment options for a patient group with limited innovation over the past decade [12] Company Strategy and Development Direction - The company aims to advance its development programs based on the upcoming data from the CORAL trial and is considering a basket trial in interstitial lung disease [23][57] - The management emphasizes the importance of FDA feedback and plans to engage with the agency based on the results of the IPF trials [11][66] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the upcoming data from the CORAL trial and the potential for positive outcomes, which would allow for continued development [20][30] - Concerns remain regarding the complexity of trials and the challenges faced in treating difficult patient populations [30] Other Important Information - The company plans to actively participate in the ATS conference, sharing insights from the RCC data set and engaging with key opinion leaders [12][52] - The management is in strategic discussions for potential partnerships, particularly for commercialization in Europe and Japan [71] Q&A Session Summary Question: What would be considered a positive readout for the CORAL trial? - A statistically significant positive trial would be the bar for success, with no unusual adverse events expected [20] Question: What are the next catalysts for the company following the CORAL readout? - The company will outline a catalyst path forward after receiving the IPF data [23] Question: What was the powered discontinuation rate for the study? - The study was powered for a 30% discontinuation rate, but the actual rate was less than 10% [29] Question: What are the thoughts on long-term patient outcomes and safety findings? - The company plans to include 52 weeks of safety data in the Phase III program and is preparing for long-term safety monitoring [68] Question: Are there any updates on the respiratory physiology study? - The study is on track to finish in the second half of the year [46] Question: What data points can be expected at ATS from the RIVER study? - The presentation will include analyses around timing of adverse events, discontinuations, and quality of life questionnaires [50]