Financial Data and Key Metrics Changes - For Q3 2025, the company reported a net loss of $11.8 million, an improvement from a net loss of $13.2 million in Q3 2024 [9] - R&D expenses decreased to $10.1 million from $11.2 million year-over-year, primarily due to reduced clinical trial work [9] - G&A expenses increased to $3.8 million from $2.9 million, mainly due to higher professional fees and personnel costs [10] - As of September 30, 2025, cash and investments totaled approximately $195 million, providing a cash runway into 2028 [10] Business Line Data and Key Metrics Changes - The company has made significant progress in its chronic cough programs, particularly in the CORAL trial for chronic cough in patients with idiopathic pulmonary fibrosis (IPF) and the RIVER trial for refractory chronic cough (RCC) [3][4] - Recent phase one studies for the IPF cough program showed no clinically meaningful changes in pharmacokinetics when nalbuphine was co-administered with standard anti-fibrotic treatments [5] Market Data and Key Metrics Changes - The company estimates approximately 228,000 patients with non-IPF interstitial lung diseases (ILD) have chronic cough, with 50-60% experiencing uncontrolled cough, significantly expanding the market opportunity [7] Company Strategy and Development Direction - The company is preparing to initiate multiple phase three trials in the first half of next year, focusing on chronic cough in both IPF and non-IPF ILD patients [8] - The strategy includes aligning with regulatory authorities and ensuring efficient clinical and commercial efforts [7][11] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the company's position, citing strong data in chronic cough conditions and a solid financial foundation to advance therapies closer to patients [11] - The management highlighted the lack of FDA-approved therapies for chronic cough, indicating a significant market opportunity [11] Other Important Information - The company plans to request a meeting with the FDA to discuss the phase three program for chronic cough in patients with IPF and non-IPF ILD [7] - Management indicated that they will apply for orphan drug designation for Haduvio in IPF [46] Q&A Session Summary Question: Inclusion/exclusion criteria for non-IPF ILD study - Management confirmed that the criteria will focus on the amount of cough and lung damage, with no current plans to exclude specific ILDs [13][15] Question: Need for additional drug-drug interaction studies - Management acknowledged the necessity for further DDI studies based on the drug's metabolism mechanisms [20] Question: Completion of the respiratory study before the end of phase two meeting - Management clarified that the study does not need to be completed before the end of phase two meeting, as they will have available data for submission [25] Question: Feedback from the CHEST meeting - Management reported strong interest from pulmonologists and investigators regarding the data presented, indicating a significant burden of chronic cough [26][27] Question: Plans for broader eligibility criteria in future trials - Management stated that they aim to keep the phase three population as broad as possible to reflect real-world patients [67] Question: Long-term data collection in phase three - Management confirmed that long-term safety data collection will be part of the phase three program, anticipating a requirement for 52 weeks of data [74]

Clinical Trials and Development - The Phase 2b CORAL trial for Haduvio demonstrated statistically significant reductions in 24-hour cough frequency of 60.2% (p<0.0001), 53.4% (p<0.0001), and 47.9% (p<0.01) for the 108 mg BID, 54 mg BID, and 27 mg BID dose groups, respectively, compared to a placebo reduction of 16.9%[135]. - The Phase 2a RIVER trial showed a 67% reduction in 24-hour cough frequency from baseline and a 57% placebo-adjusted reduction (p<0.0001) for Haduvio in patients with refractory chronic cough[144]. - The Phase 2 CANAL trial showed a statistically significant reduction in daytime cough frequency (p<0.0001) and positive results on patient-reported outcomes for Haduvio[141]. - The TIDAL study aims to assess the safety and tolerability of Haduvio in patients with IPF, with data expected in Q4 2025[140]. - The company is also developing Haduvio for chronic cough in patients with non-IPF interstitial lung disease (ILD) and plans to conduct a clinical trial for this indication[143]. - The company plans to conduct multiple clinical trials for Haduvio, including Phase 3 trials for chronic cough in patients with IPF and non-IPF ILD[183]. - The company plans to request an End-of-Phase 2 meeting with the FDA in Q4 2025 and initiate the Phase 3 program for Haduvio in the first half of 2026[139]. Financial Performance - As of September 30, 2025, the company reported an accumulated deficit of $321.5 million due to research and development and administrative expenses[147]. - The company had cash, cash equivalents, and marketable securities totaling $194.9 million as of September 30, 2025, expected to fund operations for at least 12 months[148]. - Research and development expenses for Q3 2025 decreased to $10.1 million from $11.2 million in Q3 2024, primarily due to reduced clinical development expenses[160]. - General and administrative expenses for Q3 2025 increased to $3.8 million from $2.9 million in Q3 2024, mainly due to higher professional fees and personnel-related costs[161]. - Total operating expenses for Q3 2025 were $13.9 million, a slight decrease from $14.1 million in Q3 2024[159]. - Net loss for Q3 2025 was $11.8 million, compared to a net loss of $13.2 million in Q3 2024, reflecting an improvement of $1.4 million[159]. - Research and development expenses for the nine months ended September 30, 2025, were $27.3 million, down from $30.0 million in the same period of 2024[164]. - General and administrative expenses for the nine months ended September 30, 2025, increased to $11.8 million from $9.2 million in the same period of 2024[165]. - Interest income for Q3 2025 was $2.1 million, up from $0.8 million in Q3 2024, driven by higher cash equivalents and marketable securities[162]. - The company raised approximately $115.1 million from the June 2025 Offering of 17.4 million shares at $5.75 per share[168]. - The company has not generated any revenue since inception and has incurred significant operating losses and negative cash flows[167]. - For the nine months ended September 30, 2025, net cash used in operating activities was $34.5 million, resulting from a net loss of $34.4 million[174]. - Net cash used in investing activities for the nine months ended September 30, 2025, was $63.5 million, primarily due to $116.3 million in purchases of available-for-sale marketable securities[176]. - Net cash provided by financing activities for the nine months ended September 30, 2025, was $120.7 million, mainly from cash proceeds of $108.2 million from common stock sales[178]. - The company reported a net increase in cash and cash equivalents of $22.8 million for the nine months ended September 30, 2025, compared to a decrease of $16.3 million in the same period of 2024[173]. - The company’s non-cash charges for the nine months ended September 30, 2025, included stock-based compensation expense of $3.8 million[174]. Future Outlook and Funding Needs - The company anticipates substantial expenditures in the future for the clinical development and commercialization of Haduvio[150]. - The company expects to incur substantial expenditures to advance Haduvio through clinical development and regulatory approval, requiring significant additional funding[181]. - The company believes existing cash, cash equivalents, and marketable securities will fund operations into 2028, but additional capital will be needed for full development and commercialization of Haduvio[186]. - The company has no committed external source of funds and will need to obtain further funding through various means, which may lead to dilution for stockholders[188]. - The company completed a Phase 1 drug-drug interaction study showing no clinically meaningful pharmacokinetic findings when Haduvio was co-administered with pirfenidone or nintedanib[146]. - The safety profile of Haduvio was consistent with previous trials, with discontinuation rates due to adverse events at 5.6% for Haduvio and 5.0% for placebo[142].

Financial Performance - Trevi Therapeutics ended Q3 2025 with $194.9 million in cash, cash equivalents, and marketable securities, providing a cash runway into 2028[5]. - R&D expenses decreased to $10.1 million in Q3 2025 from $11.2 million in Q3 2024, primarily due to reduced clinical development expenses[6]. - G&A expenses increased to $3.8 million in Q3 2025 from $2.9 million in Q3 2024, mainly due to higher professional fees and personnel-related expenses[7]. - Net loss for Q3 2025 was $11.8 million, an improvement from a net loss of $13.2 million in Q3 2024[8]. Clinical Development - The company is preparing to initiate a comprehensive Phase 3 program for chronic cough in patients with idiopathic pulmonary fibrosis in the first half of 2026[1]. - Trevi Therapeutics plans to submit an End-of-Phase 2 meeting request to the FDA in Q4 2025[2]. - The Phase 1 safety study for IPF patients showed no safety signals, allowing for the completion of enrollment[3]. - Topline results from the Phase 2b CORAL trial were presented at the CHEST 2025 Annual Meeting[4]. - The company intends to initiate a Phase 2b study for refractory chronic cough in the first half of 2026 following positive Phase 2a RIVER trial results[10]. Market Opportunity - There are approximately 150,000 U.S. patients with IPF, with two-thirds experiencing uncontrolled chronic cough, highlighting a significant unmet medical need[12].

Core Insights - Trevi Therapeutics is advancing its investigational therapy Haduvio for chronic cough in patients with idiopathic pulmonary fibrosis (IPF) and refractory chronic cough (RCC), with plans to initiate a comprehensive Phase 3 program in the first half of 2026 [1][5]. Financial Performance - The company reported a net loss of $11.8 million for Q3 2025, an improvement from a net loss of $13.2 million in Q3 2024 [7][13]. - Research and development (R&D) expenses decreased to $10.1 million in Q3 2025 from $11.2 million in Q3 2024, primarily due to reduced clinical development costs [4][13]. - General and administrative (G&A) expenses increased to $3.8 million in Q3 2025 from $2.9 million in Q3 2024, attributed to higher professional fees and personnel-related expenses [6][13]. - The company ended Q3 2025 with $194.9 million in cash, cash equivalents, and marketable securities, providing a cash runway into 2028 [1][4]. Clinical Development - Trevi Therapeutics is preparing to submit an End-of-Phase 2 meeting request to the FDA in Q4 2025 and plans to initiate its Phase 3 program in the first half of 2026 [2][5]. - The safety review committee for the Phase 1 TIDAL study concluded there were no safety signals, allowing for the completion of patient enrollment [5]. - Positive results from the Phase 2a RIVER trial were presented at major medical meetings, and a Phase 2b RCC study is planned for the first half of 2026 [5][9]. Market Opportunity - 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 interstitial lung disease, with 50-60% also suffering from uncontrolled chronic cough [9]. - RCC affects an estimated 2-3 million patients in the U.S., representing a significant unmet medical need as there are currently no FDA-approved therapies for these conditions [9].

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]

Core Insights - Trevi Therapeutics, Inc. is advancing its investigational therapy Haduvio™ (oral nalbuphine ER) for chronic cough associated with idiopathic pulmonary fibrosis (IPF), non-IPF interstitial lung disease (non-IPF ILD), and refractory chronic cough (RCC) [1][5] - Data from the Phase 2a RIVER trial will be presented at the European Respiratory Society (ERS) Congress 2025, highlighting the efficacy and safety of nalbuphine ER in treating RCC [1][2] Company Overview - Trevi Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on developing therapies for chronic cough, with Haduvio being the first investigational therapy to demonstrate a statistically significant reduction in cough frequency in clinical trials for both IPF and RCC patients [5][6] - Haduvio acts on the cough reflex arc as a kappa agonist and mu antagonist (KAMA), targeting opioid receptors involved in chronic cough control [5] Clinical Trial Details - The Phase 2a RIVER trial was a randomized, double-blind, placebo-controlled study designed to assess the efficacy, safety, and tolerability of nalbuphine ER in RCC patients, with treatment periods lasting 21 days and a primary endpoint focused on the mean change in 24-hour cough frequency [3][4] - The trial included a full analysis set (FAS) population, which consisted of patients who received at least one dose of the study drug and had objective cough count data [3] Market Need - RCC is characterized by a persistent cough lasting over 8 weeks despite treatment for underlying conditions, affecting approximately 2-3 million patients in the U.S. [4] - There are no FDA-approved therapies for RCC, indicating a significant unmet medical need in this patient population [4] Impact of Chronic Cough - Chronic cough in patients with IPF and non-IPF ILD is prevalent, with around 150,000 U.S. patients with IPF and 228,000 with non-IPF ILD, where 50-60% experience uncontrolled chronic cough [6] - The condition can lead to severe morbidity and a decline in quality of life, with patients potentially coughing up to 1,500 times per day [6]

Core Insights - Trevi Therapeutics Inc. (NASDAQ:TRVI) is highlighted as a promising multibagger stock, with Morgan Stanley initiating coverage with an Overweight rating and an $18 price target [1][2] Group 1: Haduvio's Market Potential - Haduvio, Trevi's extended-release formulation of nalbuphine, is being developed to treat chronic cough, addressing a significant unmet medical need in a market with limited existing therapies [2][3] - The analyst estimates that Haduvio could represent a multi-billion-dollar opportunity for Trevi, with increasing interest in the pharmaceutical sector further supporting this potential [3] Group 2: Competitive Landscape - Large pharmaceutical companies like GSK and Merck have already engaged in billion-dollar partnerships in the chronic cough treatment space, indicating that Trevi could benefit from increased attention and investment in this area [3]

Company Overview - Trevi has had a strong year as a single-asset company focused on a drug in the opioid category, specifically a mixed agonist-antagonist subcategory [3] - The drug offers the benefits of opioids, including good efficacy and safety, while minimizing addiction potential [3] - The drug has been unscheduled, allowing for broader access and potential market opportunities [3] Mechanism of Action - The unique mechanism of the drug works both centrally and peripherally, enhancing its therapeutic profile [4]

Company Overview - Trevi has had a strong year as a single-asset company focused on a drug in the opioid category, specifically a mixed agonist-antagonist subcategory [3] - The drug offers the benefits of opioids, including good efficacy and safety, while minimizing addiction potential [3] - The drug has been unscheduled, allowing for broader access and potential market opportunities [3] Mechanism of Action - The unique mechanism of the drug works both centrally and peripherally, enhancing its therapeutic profile [4]

Summary of Trevi Therapeutics FY Conference Call Company Overview - **Company**: Trevi Therapeutics (NasdaqGM:TRVI) - **Focus**: Development of a single asset drug in the opioid category, specifically a mixed agonist-antagonist that provides efficacy and safety without addiction potential [2][30] Core Points and Arguments Drug Mechanism and Indications - The drug targets three indications related to cough: 1. Chronic cough in idiopathic pulmonary fibrosis (IPF) 2. Other interstitial lung diseases (ILDs) 3. Refractory chronic cough (RCC) [3][4] - IPF is a severe condition with a poor prognosis, where 85% of patients experience chronic cough [3] - The drug has shown strong data in IPF, and the company aims to position itself as best in class against competitors [4] Competitive Landscape - There are currently no approved therapies for chronic cough associated with IPF and ILDs, creating a significant market opportunity [8] - Existing antifibrotics do not alleviate cough symptoms, leaving a gap in treatment options [8] - The company believes its drug's broad mechanism of action provides a competitive advantage over other peripheral-only mechanisms that have failed in trials [8][9] Clinical Development Plans - The company is preparing for a phase 3 trial in IPF, with a focus on maintaining a rigorous study design to manage placebo responses [12][10] - The upcoming phase 2 study for non-IPF ILDs is expected to enroll quickly due to overlapping patient populations [24][18] - The company plans to conduct a responder analysis to ensure robust data for safety and efficacy [14] Market Opportunity - Approximately 150,000 patients in the U.S. have IPF, with about two-thirds experiencing uncontrolled chronic cough [18] - Non-IPF ILDs could double the patient population, with 225,000 patients and a similar prevalence of chronic cough [18] Financial Position and Strategy - Trevi has over $200 million in cash, sufficient to fund multiple trials through late 2028 or early 2029 [43] - The company aims to leverage its capital efficiency by focusing on one drug across three indications [43] Regulatory Considerations - The company is preparing for an end of phase 2 meeting with the FDA, which will be critical for advancing its IPF program [27] - There are ongoing discussions about merging the ILD indication into the IPF program if positive results are obtained [24] Pricing Strategy - Specialty pricing is anticipated to be between $60,000 to $85,000, with expectations of inelastic demand [39] - The company plans to maintain pricing strategies across indications, including RCC, while exploring potential lower dosing options [40] Intellectual Property - Trevi has secured patents for its drug's method of treatment, with coverage extending to both IPF and RCC [41][42] External Factors - The company does not perceive significant competitive threats from rising biotech innovation in China, as respiratory therapies are not a primary focus there [46] - Trevi is exploring the use of AI to enhance operational efficiency and decision-making as it approaches commercialization [48] Important but Overlooked Content - The company has a strong focus on maintaining a tight study design to control variability in clinical trials, particularly for refractory chronic cough [11][20] - Trevi's drug has been unscheduled by the DEA, indicating a lower risk of abuse compared to traditional opioids [30] - The company is actively monitoring regulatory changes and their potential impacts, particularly concerning the FDA's evolving landscape [51][52]