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]

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]

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].

Financial Data and Key Metrics Changes - For Q2 2025, the company reported a net loss of $12.3 million, slightly improved from a net loss of $12.4 million in Q2 2024 [13] - Research and Development (R&D) expenses decreased to $9.4 million from $10 million in the same quarter of 2024, primarily due to reduced costs in several trials [13] - General and Administrative (G&A) expenses increased to $4.3 million from $3.3 million in Q2 2024, mainly due to higher professional fees and personnel costs [14] - As of June 30, 2025, cash and investments totaled approximately $204 million, providing a cash runway into 2029 [15] Business Line Data and Key Metrics Changes - The CORAL trial for chronic cough in patients with idiopathic pulmonary fibrosis (IPF) showed a statistically significant reduction in cough frequency across all dose groups [5] - The quality of life assessment using the Lester Cough Questionnaire (LCQ) indicated significant improvements, with increases of 3.7 and 3.4 points for the 54 mg and 108 mg BID doses, respectively [6] Market Data and Key Metrics Changes - The company estimates approximately 228,000 patients with non-IPF interstitial lung diseases, with 50% to 60% experiencing uncontrolled cough, effectively doubling the market opportunity for cough treatment [10] Company Strategy and Development Direction - The company plans to initiate Phase III trials for Haduvio in the first half of next year, focusing on chronic cough in both IPF and non-IPF patients [9][11] - There is an emphasis on patient-centric development and commercialization strategies, as indicated by feedback from patient advisory boards [7] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the company's position to execute its strategy and create value following positive data from recent trials [5] - The end of Phase II meeting with the FDA is anticipated in Q4 2025, where alignment on the Phase III program will be discussed [9][30] Other Important Information - The company is preparing for a study in refractory chronic cough, with plans to initiate a Phase IIb parallel arm study in the first half of next year [11] - The company has received positive feedback from pulmonologists regarding the potential for Haduvio in treating non-IPF interstitial lung diseases [34] Q&A Session Summary Question: Progress on the respiratory depression study - Management confirmed that the respiratory safety study is ongoing with two active sites and expects to have data for the end of Phase II meeting [20][22] Question: Key questions for the upcoming FDA meeting - The focus will be on data from the CORAL trial, adequacy of the program, and specifics of the Phase III protocol [30][31] Question: Parallel design for the non-IPF ILD study - Management indicated that the study will have minimum criteria for enrollment, allowing for a broader patient base while focusing on fibrosis and cough [46][50] Question: Tolerability and adverse events from the CORAL trial - Management expressed satisfaction with the CORAL data and indicated no changes are anticipated going forward [52] Question: Dose selection for the Phase III study - The 54 mg BID dose is expected to be a key dose moving forward based on its performance in the CORAL trial [57] Question: Additional data from the CORAL trial - Management confirmed that the LCQ data complements objective cough data and will be discussed in future meetings [63][64] Question: Commercialization plans and partnering - The company is focused on its Phase III program in the U.S. and may consider partnerships in Europe or Japan [104]

[Registrant Information](index=1&type=section&id=Registrant%20Information) This section provides basic identification details for Trevi Therapeutics, Inc [Registrant Details](index=1&type=section&id=Registrant%20Details) This section provides the basic identification details of Trevi Therapeutics, Inc., including its filing type, stock exchange listing, and filer status for the quarterly period ended June 30, 2025 - **Filing**: Quarterly Report on **Form 10-Q** for the period ended June 30, 2025[2](index=2&type=chunk) - **Registrant**: **TREVI THERAPEUTICS, INC.** (**Delaware**)[2](index=2&type=chunk) Securities Registered | Title of each class | Trading Symbol(s) | Name of each exchange on which registered | | :------------------ | :---------------- | :---------------------------------------- | | Common Stock, $0.001 par value per share | TRVI | The **Nasdaq Stock Market LLC** | Filer Status | Filer Type | | :----------- | | **Non-accelerated filer** ☒ | | **Smaller reporting company** ☒ | - As of July 31, 2025, the registrant had **121,776,855** shares of **common stock outstanding**[4](index=4&type=chunk) [Cautionary Note Regarding Forward-Looking Statements and Industry Data](index=3&type=section&id=CAUTIONARY%20NOTE%20REGARDING%20FORWARD-LOOKING%20STATEMENTS%20AND%20INDUSTRY%20DATA) This section warns that the report contains forward-looking statements and industry data with inherent risks and limitations [Forward-Looking Statements and Data Limitations](index=3&type=section&id=Forward-Looking%20Statements%20and%20Data%20Limitations) This section warns readers that the report contains forward-looking statements subject to substantial risks and uncertainties, meaning actual results could differ materially. It also highlights that industry and market data, including estimates for Haduvio, are based on assumptions and have limitations, and are not independently verified - All statements, other than statements of historical fact, are **forward-looking** and involve substantial risks and uncertainties[5](index=5&type=chunk) - Actual results or events could differ materially from the plans, intentions, and expectations disclosed in **forward-looking** statements[6](index=6&type=chunk) - Important factors that could cause actual results to differ materially are included in the '**Risk Factors**' section[6](index=6&type=chunk) - The report includes statistical and other industry and market data obtained from third-party publications and internal estimates, which involve a number of assumptions and limitations[8](index=8&type=chunk) - **Forward-looking** statements include plans for **clinical trials** (**Phase 3 IPF**, **Phase 1 TIDAL**, **non-IPF ILD**, **RCC**), **commercialization**, **regulatory approvals**, **funding**, **expenses**, **competitive position**, and **collaborations**[10](index=10&type=chunk) [Risk Factor Summary](index=4&type=section&id=RISK%20FACTOR%20SUMMARY) This section summarizes principal investment risks, including financial losses, funding needs, and product development challenges [Principal Investment Risks](index=4&type=section&id=Principal%20Investment%20Risks) This section summarizes the key speculative and risky factors for investors, including the company's history of significant losses and expected future losses, the critical need for additional funding, and the sole dependence on the successful development and commercialization of Haduvio. It also highlights risks related to clinical trials, regulatory approvals, competition, and intellectual property - The company has incurred **significant losses** since inception and expects to continue incurring increasing losses, with no assurance of achieving or maintaining profitability[12](index=12&type=chunk) - **Substantial additional funding** is required; failure to raise capital could force delays, reductions, or abandonment of product development or **commercialization** efforts[12](index=12&type=chunk) - The business is substantially harmed if **Haduvio**, the **sole product candidate**, fails to complete **clinical development**, obtain marketing approval, or be successfully **commercialized**, or if significant delays occur[12](index=12&type=chunk) - **Clinical trials** involve lengthy, expensive, and uncertain processes, with outcomes not always predictive of later success, and potential for delays in patient enrollment[12](index=12&type=chunk) - **Haduvio's** active ingredient, nalbuphine, carries an **opioid class label warning** for **serious respiratory depression**, which will likely apply to **Haduvio** if approved[12](index=12&type=chunk) - The company faces competition from others developing or **commercializing** products, and relies on **third parties** for **clinical trials** and manufacturing, including a **single supplier** for the active ingredient[12](index=12&type=chunk) - Failure to comply with **intellectual property** licenses or obtain sufficient patent protection could lead to loss of critical rights or allow competitors to develop similar products[13](index=13&type=chunk) - The **significant number of shares** underlying outstanding **warrants** could negatively affect the **market price** of common stock and make future **equity financings** more difficult[13](index=13&type=chunk) [PART I. FINANCIAL INFORMATION](index=8&type=section&id=PART%20I.%20FINANCIAL%20INFORMATION) This part presents the company's unaudited condensed consolidated financial statements and management's discussion and analysis [Item 1. Condensed Consolidated Financial Statements (Unaudited)](index=8&type=section&id=Item%201.%20Condensed%20Consolidated%20Financial%20Statements%20(Unaudited)) This section presents the unaudited condensed consolidated financial statements for Trevi Therapeutics, Inc. for the three and six months ended June 30, 2025 and 2024, including balance sheets, statements of comprehensive loss, statements of stockholders' equity, statements of cash flows, and detailed notes explaining accounting policies and specific financial line items [Condensed Consolidated Balance Sheets](index=8&type=section&id=Condensed%20Consolidated%20Balance%20Sheets) This section presents the company's financial position at specific dates, detailing assets, liabilities, and stockholders' equity Key Balance Sheet Data (Amounts in thousands) | Metric | June 30, 2025 (Unaudited) | December 31, 2024 | | :--------------------------------- | :-------------------------- | :------------------ | | **Total assets** | \$208,339 | \$110,900 | | **Cash and cash equivalents** | \$117,058 | \$34,097 | | **Marketable securities** | \$86,827 | \$73,525 | | **Total current assets** | \$207,228 | \$109,428 | | **Total liabilities** | \$9,846 | \$11,256 | | **Total stockholders' equity** | \$198,493 | \$99,644 | | **Accumulated deficit** | \$(309,686) | \$(287,045) | - **Total assets** increased by **\$97.4 million** from December 31, 2024, to June 30, 2025, primarily driven by increases in **cash and cash equivalents** and **marketable securities**[18](index=18&type=chunk) [Condensed Consolidated Statements of Comprehensive Loss](index=9&type=section&id=Condensed%20Consolidated%20Statements%20of%20Comprehensive%20Loss) This section details the company's financial performance over periods, including revenues, expenses, and net loss Key Comprehensive Loss Data (Amounts in thousands) | Metric | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :--------------------------------------- | :------------------------------- | :------------------------------- | :----------------------------- | :----------------------------- | | Research and development expenses | \$9,389 | \$10,021 | \$17,200 | \$18,825 | | General and administrative expenses | \$4,333 | \$3,268 | \$7,992 | \$6,370 | | Total operating expenses | \$13,722 | \$13,289 | \$25,192 | \$25,195 | | **Net loss** | \$(12,301) | \$(12,352) | \$(22,641) | \$(23,254) | | **Basic and diluted net loss per common share** | \$(0.09) | \$(0.12) | \$(0.18) | \$(0.23) | | **Comprehensive loss** | \$(12,350) | \$(12,369) | \$(22,678) | \$(23,309) | - **Net loss** for the six months ended June 30, 2025, **decreased by \$613 thousand** compared to the same period in 2024[21](index=21&type=chunk) - **Interest income, net**, increased to **\$2.5 million** for the six months ended June 30, 2025, from **\$1.9 million** in the prior year period[21](index=21&type=chunk) [Condensed Consolidated Statements of Stockholders' Equity](index=10&type=section&id=Condensed%20Consolidated%20Statements%20of%20Stockholders'%20Equity) This section outlines changes in the company's equity accounts over periods, including common stock, additional paid-in capital, and accumulated deficit Stockholders' Equity Changes (Amounts in thousands) | Metric | Balance at March 31, 2025 | Issuance of common stock under offering, less issuance costs | Net loss | Balance at June 30, 2025 | | :--------------------------------------- | :------------------------ | :----------------------------------------- | :--------- | :----------------------- | | **Common Stock** (Amount) | \$100 | \$20 | — | \$122 | | **Additional Paid-in Capital** | \$396,669 | \$107,373 | — | \$508,033 | | **Accumulated Deficit** | \$(297,385) | — | \$(12,301) | \$(309,686) | | **Total Stockholders' Equity** | \$99,457 | \$107,39