Core Insights - Trevi Therapeutics, Inc. announced the acceptance of two abstracts for presentation at the CHEST 2025 Annual Meeting, focusing on the efficacy and safety results of nalbuphine ER for chronic cough treatment in patients with idiopathic pulmonary fibrosis (IPF) and refractory chronic cough (RCC) [1][5] Group 1: Clinical Trials - The Phase 2b CORAL trial evaluated nalbuphine ER in three doses (27 mg, 54 mg, and 108 mg twice daily) against placebo for chronic cough in IPF patients over a 6-week period, with 165 patients randomized [3] - The primary efficacy endpoint was the relative change in 24-hour cough frequency, measured by an objective cough monitor, comparing nalbuphine ER to placebo at the end of Week 6 [3] - The Phase 2a RIVER trial assessed nalbuphine ER's efficacy, safety, and tolerability in RCC patients through a crossover study design, with each treatment period lasting 21 days [4] Group 2: Patient Population and Unmet Need - There are approximately 150,000 patients with IPF in the U.S., with two-thirds experiencing uncontrolled chronic cough, and around 228,000 patients with non-IPF ILD, with 50-60% also facing uncontrolled chronic cough [6] - Chronic cough can lead to significant morbidity and mortality, including increased respiratory hospitalizations and a decline in quality of life [6] - RCC affects an estimated 2-3 million patients in the U.S., characterized by a persistent cough lasting over 8 weeks despite treatment for underlying conditions, indicating a high unmet medical need [6] Group 3: Product Information - Trevi Therapeutics is developing Haduvio™ (oral nalbuphine ER) as a potential treatment for chronic cough in IPF, non-IPF ILD, and RCC, which has shown statistically significant reductions in cough frequency in clinical trials [5] - Nalbuphine acts on the cough reflex arc as a kappa agonist and mu antagonist, targeting opioid receptors involved in cough control [5]

Financial Data and Key Metrics Changes - The company completed H1 2025 with cash of CHF 2.3 million, providing a runway through mid-2026 [6] - Income decreased by $100,000 in Q2 2025 compared to Q2 2024, amounting to $100,000, primarily due to the completion of the funded research phase with Indivior [18] - R&D expenses of $200,000 in Q2 2025 decreased by $100,000 compared to Q2 2024, mainly due to the completion of the research phase with Indivior [19] - G&A expenses of $500,000 decreased by $100,000 in Q2 2025 compared to Q2 2024, primarily due to decreased legal fees [19] - Current liabilities increased by $300,000 compared to December 2024, primarily due to increased payables [20] Business Line Data and Key Metrics Changes - The GABA B PAM program has made significant progress, with IND enabling studies completed by the partner Indivior for substance use disorders [21] - The company has advanced its independent GABA B PAM program for chronic cough and is ready to start IND enabling studies, subject to securing financing [21] - The repositioning of diproglurant for brain injury recovery has been initiated, with an exclusive license agreement for mGluR5 inhibitors [5] Market Data and Key Metrics Changes - The chronic cough market presents a large unmet medical need, with current treatments ineffective in 30% of patients and only moderately effective in up to 60% [12] - The company believes that GABA B PAMs could offer superior efficacy in chronic cough patients compared to current standards of care [12] Company Strategy and Development Direction - The company is focused on advancing its GABA B PAM program and has regained rights to its mGluR2 positive allosteric modulator program [4] - The strategic objective includes validating partnerships with industry and supportive investors while maintaining a strong balance sheet [21] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the renewed interest in the neuropsychiatry space, highlighting recent transactions and the potential for Neurosterics and Stellicla [25] - The company is actively pursuing financing strategies for Stellicla, which is focused on patient stratification technology [26] Other Important Information - The company has invested in Stellicla, which has developed a precision medicine platform for neurodevelopmental disorders [5] - The IND enabling studies for the GABA B PAM program are planned to start this year, with promising preclinical data [16] Q&A Session Summary Question: Recent developments in the neuropsychiatry space and implications for Neurosterics and Stellicla - Management noted renewed excitement in the neuropsychiatry space and highlighted the successful financing of Neurosterics [25][26] Question: Insights into long-acting injectable formulations for Neurosterics - Management indicated that while they cannot speculate, there is potential for longer-acting formulations in the m4 PAM space due to compliance issues [30][31] Question: Ideal target patient population for the chronic cough program - Management stated that the GABA B PAMs were selected to maximize the range of chronic cough patients, focusing on centrally acting compounds [33]

Core Viewpoint - Trevi Therapeutics, Inc. is advancing its investigational therapy Haduvio™ for chronic cough associated with idiopathic pulmonary fibrosis (IPF), non-IPF interstitial lung disease (non-IPF ILD), and refractory chronic cough (RCC) [1][4]. Company Overview - Trevi Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on developing Haduvio™ (oral nalbuphine ER) for chronic cough treatment [4]. - Haduvio is the first investigational therapy to demonstrate a statistically significant reduction in cough frequency in clinical trials for patients with IPF chronic cough and RCC [4]. Market Context - Chronic cough affects up to 85% of patients with IPF, with approximately 150,000 patients in the U.S. suffering from this condition [5]. - Patients with chronic cough may cough up to 1,500 times per day, leading to severe impacts on their quality of life and potential disease progression [5]. - There are currently no approved therapies for chronic cough in IPF patients, and existing off-label treatments offer minimal benefits [5]. Refractory Chronic Cough - RCC, affecting around 2-3 million patients in the U.S., is characterized by a persistent cough lasting more than 8 weeks despite treatment for underlying conditions [6]. - The condition is associated with significant social and economic burdens, including complications like urinary incontinence and sleep disruption [6]. Upcoming Conferences - Trevi Therapeutics will participate in several healthcare conferences in September 2025, including the Wells Fargo Healthcare Conference and the Morgan Stanley Global Healthcare Conference [2][3].

Core Viewpoint - Trevi Therapeutics, Inc. is advancing its investigational therapy Haduvio™ for chronic cough associated with idiopathic pulmonary fibrosis (IPF), non-IPF interstitial lung disease (non-IPF ILD), and refractory chronic cough (RCC), with upcoming participation in key biotech conferences [1][2]. Company Overview - Trevi Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on developing Haduvio™ (oral nalbuphine ER) for chronic cough treatment [2][5]. - Haduvio is the first investigational therapy to demonstrate a statistically significant reduction in cough frequency in clinical trials for patients with IPF chronic cough and RCC [2][5]. Industry Context - Chronic cough affects up to 85% of patients with IPF, with approximately 150,000 patients in the U.S. suffering from this condition [3]. - Patients with chronic cough may cough up to 1,500 times per day, leading to severe health impacts, including disease progression and reduced quality of life [3]. - There are currently no approved therapies for chronic cough in IPF patients, and existing off-label treatments offer minimal benefits [3]. - Refractory chronic cough, affecting around 2-3 million patients in the U.S., is characterized by a persistent cough lasting over 8 weeks without approved therapies [4].

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, 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]

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 [12] - R&D expenses decreased to $7.8 million from $8.8 million in the same quarter of 2024, primarily due to reduced costs related to a human abuse potential study [12] - G&A expenses increased to $3.7 million from $3.1 million in Q1 2024, mainly due to higher personnel-related expenses [13] - As of March 31, 2025, cash and investments totaled $103.3 million, providing a runway into Q4 2026 [13] Business Line Data and Key Metrics Changes - The Phase 2a RIVER trial in refractory chronic cough (RCC) patients showed a 57% placebo-adjusted reduction in cough frequency, achieving a p-value of less than 0.0001 [6] - The Phase 2b CORAL trial for chronic cough in idiopathic pulmonary fibrosis (IPF) patients completed enrollment with approximately 160 patients across 10 countries [7] Market Data and Key Metrics Changes - RCC affects approximately 2 to 3 million patients in the U.S. with no approved therapies currently available [4] - The company is preparing for the release of top-line data from the CORAL trial this quarter, which is expected to provide insights into treatment options for IPF patients [8] Company Strategy and Development Direction - The company aims to advance its development programs based on the data from the ongoing trials, particularly focusing on chronic cough conditions in both RCC and IPF [8] - There is an emphasis on the importance of the central mechanism underlying neurogenic chronic cough conditions, which differentiates the company's approach from others in the market [6] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism regarding the FDA's responsiveness and guidance, which is critical for the development programs [9] - The company plans to be active at the upcoming ATS conference, sharing insights from the RCC data set and engaging with key opinion leaders [10] Other Important Information - The company has received positive feedback from the FDA regarding a Type C request, which is crucial for the development of their programs [9] - The company is considering strategic partnerships for commercialization in Europe and Japan, depending on the data and timing [68] Q&A Session Summary Question: What would be considered a positive readout for the CORAL trial? - A statistically significant positive trial would be necessary for continued development, with no unusual adverse events expected [17][19] Question: What are the next catalysts for the company following the CORAL readout? - The company plans to outline future catalysts after receiving the IPF data, which will inform their path forward [21] Question: Can you clarify the discontinuation rate powered for the study? - The study was powered for a 30% discontinuation rate, but the actual rate was less than 10% [28] Question: What are the long-term patient safety monitoring protocols? - The company plans to include 52 weeks of safety data in their Phase III program, as advised by the FDA [65] Question: What are the trends observed in the RIVER study regarding patient baseline characteristics? - It is too early to determine specific trends, but the drug showed significant efficacy across a broad patient population [71][72]

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) [4][5] - Haduvio is the first therapy in clinical development to demonstrate a statistically significant reduction in chronic cough for both IPF and RCC patients [4] Market Need - Chronic cough affects up to 85% of the 140,000 U.S. IPF patients, leading to severe impacts on their quality of life, including social, physical, and psychological decline [5] - Refractory chronic cough, affecting approximately 2-3 million patients in the U.S., has no approved therapies and is characterized by a persistent cough lasting over 8 weeks despite treatment for underlying conditions [6] Upcoming Events - Trevi will participate in several investor conferences in April 2025, including: - 24th Annual Needham Virtual Healthcare Conference on April 7, with a corporate presentation by Jennifer Good, President and CEO [2] - Jones Healthcare and Technology Innovation Conference on April 9, with a presentation by Jennifer Good [3] - Piper Sandler Spring Biopharma Symposium on April 16-17, featuring Jennifer Good and James Cassella [4] Product Details - Haduvio acts on the cough reflex arc as a kappa agonist and mu antagonist, targeting opioid receptors involved in cough hypersensitivity [4] - The safety and efficacy of Haduvio have not yet been evaluated by any regulatory authority [7]