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]

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]

PART I. FINANCIAL INFORMATION This section presents Trevi Therapeutics' unaudited condensed consolidated financial information, covering statements, management's discussion, market risk, and controls [Item 1. Condensed Consolidated Financial Statements (Unaudited)](index=8&type=section&id=Item%201.%20Condensed%20Consolidated%20Financial%20Statements%20(Unaudited)) This section presents Trevi Therapeutics' unaudited condensed consolidated financial statements, including balance sheets, comprehensive loss, equity, and cash flows, with detailed notes for **Q1 2025** and **FY 2024** [Condensed Consolidated Balance Sheets](index=8&type=section&id=Condensed%20Consolidated%20Balance%20Sheets) This section presents the unaudited condensed consolidated balance sheets for Trevi Therapeutics, Inc. as of March 31, 2025, and December 31, 2024 | Metric (in thousands) | March 31, 2025 | December 31, 2024 | Change | % Change | | :-------------------- | :------------- | :---------------- | :----- | :------- | | Cash and cash equivalents | $19,374 | $34,097 | $(14,723) | -43.18% | | Marketable securities | $83,883 | $73,525 | $10,358 | 14.09% | | Total current assets | $105,621 | $109,428 | $(3,807) | -3.48% | | Total assets | $107,004 | $110,900 | $(3,896) | -3.51% | | Total current liabilities | $6,866 | $10,509 | $(3,643) | -34.67% | | Total liabilities | $7,547 | $11,256 | $(3,709) | -32.95% | | Total stockholders' equity | $99,457 | $99,644 | $(187) | -0.19% | [Condensed Consolidated Statements of Comprehensive Loss](index=9&type=section&id=Condensed%20Consolidated%20Statements%20of%20Comprehensive%20Loss) This section presents the unaudited condensed consolidated statements of comprehensive loss for the three months ended March 31, 2025, and 2024 | Metric (in thousands) | Three Months Ended March 31, 2025 | Three Months Ended March 31, 2024 | Change | % Change | | :-------------------- | :-------------------------------- | :-------------------------------- | :----- | :------- | | Research and development | $7,811 | $8,804 | $(993) | -11.28% | | General and administrative | $3,659 | $3,102 | $557 | 17.96% | | Total operating expenses | $11,470 | $11,906 | $(436) | -3.66% | | Loss from operations | $(11,470) | $(11,906) | $436 | -3.66% | | Interest income, net | $1,125 | $998 | $127 | 12.73% | | Net loss | $(10,340) | $(10,902) | $562 | -5.15% | | Basic and diluted net loss per common share | $(0.09) | $(0.11) | $0.02 | -18.18% | [Condensed Consolidated Statements of Stockholders' Equity](index=10&type=section&id=Condensed%20Consolidated%20Statements%20of%20Stockholders'%20Equity) This section presents the unaudited condensed consolidated statements of stockholders' equity for the three months ended March 31, 2025 | Metric (in thousands) | Balance at Dec 31, 2024 | Stock-based Compensation | Stock Option Exercise | Warrant Exercise | Net Loss | Balance at Mar 31, 2025 | | :-------------------- | :---------------------- | :----------------------- | :-------------------- | :--------------- | :------- | :---------------------- | | Common Stock (Amount) | $94 | — | — | $6 | — | $100 | | Additional Paid-in Capital | $386,534 | $1,208 | $718 | $8,214 | — | $396,669 | | Accumulated Deficit | $(287,045) | — | — | — | $(10,340) | $(297,385) | | Total Stockholders' Equity | $99,644 | $1,208 | $718 | $8,220 | $(10,340) | $99,457 | [Condensed Consolidated Statements of Cash Flows](index=11&type=section&id=Condensed%20Consolidated%20Statements%20of%20Cash%20Flows) This section presents the unaudited condensed consolidated statements of cash flows for the three months ended March 31, 2025, and 2024 | Cash Flow Activity (in thousands) | Three Months Ended March 31, 2025 | Three Months Ended March 31, 2024 | Change | | :-------------------------------- | :-------------------------------- | :-------------------------------- | :----- | | Net cash used in operating activities | $(13,477) | $(10,467) | $(3,010) | | Net cash used in investing activities | $(9,951) | $(8,091) | $(1,860) | | Net cash provided by (used in) financing activities | $8,705 | $(28) | $8,733 | | Net decrease in cash and cash equivalents | $(14,723) | $(18,586) | $3,863 | | Cash and cash equivalents at end of period | $19,374 | $13,811 | $5,563 | [Notes to Unaudited Condensed Consolidated Financial Statements](index=12&type=section&id=Notes%20to%20Unaudited%20Condensed%20Consolidated%20Financial%20Statements) This section provides detailed notes explaining the accounting policies, financial instruments, and other relevant financial information supporting the unaudited condensed consolidated financial statements [Note 1. Nature of the Business](index=12&type=section&id=Note%201.%20Nature%20of%20the%20Business) Trevi Therapeutics is a clinical-stage biopharmaceutical company developing **Haduvio** for chronic cough in **IPF**, **non-IPF ILD**, and **RCC**, utilizing a **kappa agonist and mu antagonist** mechanism - Trevi Therapeutics is a clinical-stage biopharmaceutical company developing **Haduvio** (oral nalbuphine ER) for chronic cough in **IPF**, **non-IPF ILD**, and **RCC**[29](index=29&type=chunk) - **Haduvio's** mechanism of action is a **kappa agonist and mu antagonist** (**KAMA**), targeting opioid receptors to control chronic cough, potentially mitigating abuse risk associated with mu-opioid agonists[30](index=30&type=chunk) [Note 2. Summary of Significant Accounting Policies](index=12&type=section&id=Note%202.%20Summary%20of%20Significant%20Accounting%20Policies) This note outlines significant accounting policies for interim financial statements, covering basis of presentation, estimates, and recently adopted pronouncements for various financial items - The financial statements are prepared in accordance with **GAAP** for interim financial information and **SEC** rules, with certain information condensed or omitted[31](index=31&type=chunk) - Significant estimates include **R&D** expenses, valuation of stock-based awards, and valuation allowance for deferred tax assets[34](index=34&type=chunk) - The Company adopted **ASU 2023-07 (Segment Reporting)** for the fiscal year beginning **January 1, 2024**, resulting in incremental disclosures[73](index=73&type=chunk) - The Company is evaluating the impact of **ASU 2024-03 (Disaggregation of Income Statement Expenses)** and **ASU 2023-09 (Improvements to Income Tax Disclosures)**, effective for fiscal years beginning after **December 15, 2026**, and **December 15, 2024**, respectively[74](index=74&type=chunk)[75](index=75&type=chunk) [Note 3. Marketable Securities](index=19&type=section&id=Note%203.%20Marketable%20Securities) This note details the Company's available-for-sale marketable securities by type and maturity, including amortized cost, unrealized gains/losses, and fair value as of **March 31, 2025** Marketable Securities by Type (March 31, 2025) | Type of security | Amortized Cost ($ thousands) | Gross Unrealized Gains ($ thousands) | Gross Unrealized Losses ($ thousands) | Estimated Fair Value ($ thousands) | | :--------------- | :--------------------------- | :----------------------------------- | :------------------------------------ | :------------------------------- | | U.S. treasury securities | 24,887 | 44 | (3) | 24,928 | | Commercial paper | 22,609 | 3 | (5) | 22,607 | | Corporate bonds | 17,434 | 26 | (1) | 17,459 | | U.S. government agency securities | 13,325 | 16 | (5) | 13,336 | | Asset backed securities | 5,555 | — | (2) | 5,553 | | Total marketable securities | 83,810 | 89 | (16) |

Trevi Therapeutics Reports First Quarter 2025 Financial Results and Provides Business Updates Completed enrollment and last patient last visit in the Phase 2b CORAL trial in IPF patients with chronic cough; topline results continue to be expected in the second quarter of 2025 Exhibit 99.1 Announced positive topline results from the Phase 2a RIVER trial in patients with refractory chronic cough Management to host a conference call and webcast today at 4:30 p.m. ET • Enrollment was completed in February 2025 ...

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]