Trevi Therapeutics, Inc.

Good afternoon, and welcome to the Trevi Therapeutics third quarter 2025 earnings conference call. At this time, all participants will be in listen-only mode. Should you need assistance, please signal a conference specialist by pressing the star key followed by zero. After today's presentation, there will be an opportunity to ask questions. To ask a question, you may press star, then one on your phone. To withdraw your question, please press star, then two. Please note this event is being recorded. Various remarks that management makes during this conference call about the company's future expectations, plans, and prospects constitute forward-looking statements for purposes of the Safe Harbor provisions under the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the risk factors section of the company's most recent quarterly report on Form 10-K, which the company filed with the SEC this afternoon. In addition, any forward-looking statements represent the company's views only as of today and should not be relied upon as representing the company's views as of any subsequent date. While the company may elect to update these forward-looking statements at some point in the future, the company specifically disclaims any obligation to do so if its views change. I would now like to turn the conference over to Jennifer Good, Trevi's President and CEO. Please go ahead.

Good afternoon, and thank you for joining us for our third quarter 2025 earnings call and business update. Joining me today on this call are my colleagues, Dr. James Casella, our Chief Development Officer, and Farrell Simon, our Chief Commercial Officer. I will make some comments on the business and financial results, then the team is happy to answer any questions you may have. The first half of this year was a major inflection point for Trevi, with positive data readouts in both the CORAL trial for chronic cough in patients with idiopathic pulmonary fibrosis, or IPF, and the RIVER trial for patients with refractory chronic cough, or RCC. We recently presented these results at CHESS, and it was great to see the interest from leading thought leaders and community pulmonologists. As a result of these strong data, we were able to raise approximately $115 million in June, giving us cash runway into 2028 and an ability to execute on the next clinical studies for each indication. It is an exciting place to be in our journey, and we have not wasted any time in moving forward. Let me provide a brief update on what the team has been up to in each of our chronic cough indications. We have recently completed a couple of important Phase I studies to advance our IPF COF program. The FDA requested we conduct a drug-drug interaction study looking at any potential PK interactions when nalbucine ER is co-administered with perfenadone or nintenadib, which are antifibrotics and the standard of care taken by patients with IPF and other progressive fibrotic diseases. We recently received the data from this study, and we are pleased that there were no clinically meaningful changes in the pharmacokinetics of any of the drug combinations used in this study. We will publish these data in the future, but we did not see anything that will impact the dosing in our Phase III program. We also made good progress on our title study, which is Assessing Respiratory Function and Safety of Nalbufine ER in IPS Patients. Recall, this is a study requested by the FDA to investigate if there was any potential signs of respiratory depression in patients with IPF following dosing with nalbufine ER. The IPF patients in the study were housed in clinic for 10 days and given increasing dose of drug while having their oxygen, carbon dioxide levels, and respiration rate assessed for periods of time. A planned review of data by an external safety review committee in a Sentinel cohort of patients concluded that there were no safety signals in the study to date. As a result, the committee gave approval to complete enrollment for the study. We will include the available data for both the DDI and respiratory safety studies in the end of Phase II meeting package. As for the end of Phase II meeting, we expect to request that meeting in the fourth quarter of this year. The key points we are looking to discuss with the FDA are, are to gain alignment on the Phase III program for chronic cough in patients with IPF, get their input on the Phase III study design and other parameters of the protocol, as well as agree upon any other NDA-enabling work which needs to be completed. In parallel, the clinical team has been preparing to initiate the Phase III program in the first half of next year and is busy lining up key vendors and identifying sites for these global studies. We have also been preparing for a study in other non-IPF interstitial lung diseases, or ILD. This population will include non-IPF ILD patients that have lung fibrosis and chronic cough. We estimate there are approximately 228,000 of these patients, with 50% to 60% having uncontrolled cough. This more than doubles the market opportunity of IPF chronic cough, and these patients are primarily seen by the same pulmonologists that see IPF patients. This keeps our clinical and commercial efforts efficient and creates synergies. We plan to request a meeting with the FDA after we align on the IPF pivotal program to discuss our study design and protocol for this indication as well. Once we have FDA input, we will be prepared to initiate this study. Finally, we have been working on the next study in refractory chronic cough. We expect that study to be a Phase IIb parallel-arm dose-ranging study and are planning to initiate that study in the first half of next year. We are drafting the protocol and identifying sites for this study as well. So, as you can see, there is a lot of planning going on at TREVI, as well as preparation work to align with the regulatory authorities and initiate multiple trials in the first half of next year. This takes time to ensure that we get these trials right. We will provide updates on next steps as we gain alignment and have line of sight to study starts. I will now provide a quick review of the financial results for the quarter. The full financial results for the three months ended September 30, 2025 can be found in our press release issued ahead of this call and our 10-Q, which was filed with the SEC today after the market closed. For the third quarter of 2025, we reported a net loss of $11.8 million compared to a net loss of $13.2 million for the same quarter in 2024. R&D expenses decreased to $10.1 million during the third quarter of 2025 from $11.2 million in the same quarter last year. The reduction was primarily due to decreased clinical trial work in which those trials were actively enrolling in the prior year and reported data in the first half of this year. This was partially offset by increased costs related to our recently completed Phase I studies and personnel and related expenses. G&A expenses increased to $3.8 million during the third quarter of 2025 compared to $2.9 million in the same quarter of last year, primarily due to an increase in professional fees and personnel and related expenses. The increased professional fees were primarily due to increased costs as we continue to prepare for compliance with SOC 404B regulations. As of September 30, 2025, our cash and investments totaled approximately $195 million. Our cash and investments gives us cash runway into 2028, subject to finalizing the development for each of our indications. We expect to be able to fund two Phase III trials of Heduvial for the treatment of chronic cough in patients with IPF, along with a long-term extension for those trials. Our planned Phase IIb-3 trial in chronic cough in patients with non-IPF-ILD, our next trial in patients with RCC, and our ongoing Phase I supportive studies. So, in closing, Trevi is positioned with strong data in two serious chronic cough conditions and is preparing to advance into the next stage of development for each of the three chronic cough indications. Chronic cough is a debilitating condition for which there are currently no FDA-approved therapies. Also, the company is financially strong, with enough cash to complete the next stage of development work to potentially advance these therapies closer to the patients. We believe we are well positioned to execute our strategy and create meaningful shareholder value over the next couple of years. This concludes my prepared remarks. Jim Farrell and I are now happy to answer your questions. I will turn the call back over to the operator for Q&A.

We will now begin the question and answer session. To ask a question, you may press star, then 1 on your touchtone phone. If you are using a speakerphone, please pick up your handset before pressing the keys. To withdraw your question, please press star, then two. At this time, we will pause momentarily to assemble our roster. The first question comes from Ryan Deschner with Raymond James. Please go ahead.