Financial Data and Key Metrics Changes - The company ended 2025 with approximately $188 million in cash equivalents and marketable securities, providing a runway into 2028 to fund key clinical trials [18][17] - The financial position allows the company to provide top-line data in pivotal clinical trials, including the phase 2B trial in refractory chronic cough and the phase 3 trial in IPF-related chronic cough [18] Business Line Data and Key Metrics Changes - Trevi Therapeutics is preparing to initiate two pivotal phase 3 clinical trials for its lead indication, Haduvio, targeting IPF-related chronic cough, with plans to enroll approximately 300 patients in one trial and 130 in another [8][9] - The company is also planning a phase 2B trial for non-IPF interstitial lung disease (ILD) chronic cough, estimating a patient population of approximately 228,000, with 50%-60% having uncontrolled cough [11][12] Market Data and Key Metrics Changes - In the US, there are approximately 150,000 IPF patients, with two-thirds experiencing uncontrolled chronic cough, indicating a significant unmet medical need [10] - The market opportunity for non-IPF ILD chronic cough more than doubles that of IPF chronic cough, as these patients are primarily seen by the same pulmonologists [12] Company Strategy and Development Direction - The company aims to become a leader in chronic cough therapies, focusing on providing solutions for patients with high unmet needs [16] - Trevi is actively preparing for an investor and analyst day to discuss clinical and commercial strategies, as well as recent commercial learnings [15] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the clarity of the path forward for the registration trials following a positive end-of-phase 2 meeting with the FDA [6][7] - The company is optimistic about the enrollment demand for the IPF chronic cough pivotal study, noting increased awareness among physicians and patient advocacy groups [79][80] Other Important Information - The company plans to file for orphan drug designation this year, although there is skepticism about approval due to the broader applicability of the treatment [73] - Trevi is preparing for significant presentations at the American Thoracic Society meeting, where new data from various trials will be shared [15][16] Q&A Session Summary Question: Can you elaborate on the remaining phase 1 studies? - The studies are label-informative, focusing on drug-drug interactions and metabolism, and will not be rate-limiting [20][22][23] Question: Any design features for the non-IPF ILD trial? - The design will leverage learnings from the IPF trial, focusing on dose-ranging and adaptive design [24][25] Question: Will there be any discussions about orphan drug designation? - The company plans to file for orphan drug designation after aligning with the FDA on the program [73] Question: What are the expectations for recruitment in the phase 3 IPF cough trial? - Enrollment is expected to take about a year, with 80 to 100 sites primarily in the US [102] Question: Will additional phase 1 drug-drug interaction studies be needed? - It depends on the timing of other drug approvals, but it is not seen as a barrier [104] Question: What is the anticipated placebo effect in the longer trial? - The company expects to be well-powered to handle the placebo response based on previous studies [97] Question: How will the company broaden the patient population for the phase 3 trial? - The trial will include patients on background anti-fibrotic medications and will not have a cough count requirement [120]

Financial Data and Key Metrics Changes - The company ended 2025 with approximately $188 million in cash equivalents and marketable securities, providing a runway into 2028 to fund key clinical trials [15][14] - The cash runway is expected to support top-line data in pivotal phase 3 clinical trials for IPF-related chronic cough and phase 2B trials for RCC and non-IPF ILD [15] Business Line Data and Key Metrics Changes - The company is preparing to initiate two pivotal phase 3 clinical trials for Haduvio in IPF-related chronic cough, with the first trial expected to start in Q2 2026 [6][4] - The second phase 3 trial is anticipated to begin in the second half of 2026, focusing on a 12-week primary efficacy endpoint [6][7] Market Data and Key Metrics Changes - In the US, there are approximately 150,000 IPF patients, with two-thirds experiencing uncontrolled chronic cough, indicating a significant unmet medical need [8] - The market opportunity for non-IPF ILD patients is estimated to be around 228,000, with 50%-60% suffering from uncontrolled cough, effectively doubling the market potential [10] Company Strategy and Development Direction - The company aims to become a leader in chronic cough treatment, focusing on developing therapies for patients with high unmet needs [12] - The strategy includes conducting adaptive phase 2B trials for non-IPF ILD and refractory chronic cough, with plans to file supplemental NDAs for these indications [9][10] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the clarity of the path forward for registration trials following positive FDA interactions [5][4] - The company is optimistic about the enrollment demand for the IPF chronic cough pivotal study, citing increased awareness among physicians and patient advocacy groups [78][77] Other Important Information - The company plans to hold an investor and analyst day on May 7, 2026, to discuss clinical and commercial strategies in detail [12] - The company will also participate in the American Thoracic Society meeting, sharing new data from various trials [12] Q&A Session Summary Question: Can you elaborate on the remaining phase 1 studies discussed with the FDA? - The studies are label-informative, focusing on drug-drug interactions and metabolism, which are not rate-limiting and can be conducted in parallel with phase 3 trials [17][19] Question: What design features are being aligned with the FDA for the non-IPF ILD trial? - The company plans to propose an adaptive phase 2B trial design, leveraging insights from the IPF end-of-phase 2 meeting [20][22] Question: Will the label dose in RCC be the same as in IPF? - The company is exploring the dosing strategy and may require additional IP if the dosing differs significantly [58] Question: What are the expectations for recruitment pace in the phase 3 IPF cough trial? - The company anticipates a one-year enrollment period for the phase 3 trial, focusing on 80 to 100 sites primarily in the US [102] Question: Will there be any pre-specified analyses for dyspnea and exacerbations in the phase 3 trial? - The company will track various metrics related to cough, breathlessness, and other patient concerns, but the primary focus remains on cough [116][115]

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]