Trevi Therapeutics, Inc.

Good afternoon, and welcome to the Trevi Therapeutics second 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 telephone. 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 factor section of the company's most recent quarterly report on Form 10-Q, 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, even 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 second quarter 2025 earnings call and business update. Joining me today on this call are my colleagues Lisa Delfini, Trevi's Chief Financial Officer, Dr. James Casella, our Chief Development Officer, and Farrell Simon, our Chief Commercial Officer. Lisa and I will make some comments on the business and financial results, then the team is happy to answer any questions that you may have. The first half of this year has been 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. As a result of this strong data, we were able to raise approximately $115 million in capital for total cash and investments at the end of June of approximately $204 million. This gives us strong runway to execute against several important clinical milestones in each of our programs. It is an exciting place to be in our journey, and we believe we are well positioned to execute our strategy and create value. Let me provide a brief update on what we have been up to this summer. As you all know, the top line results from our CORAL trial were announced in early June, with Heduvio meeting the primary endpoint with a statistically significant reduction in 24-hour cough frequency across all dose groups studied. Since reporting our top line data, we have received the full data set from the trial and can confirm that the data across the secondary endpoints were consistent with the top line results. Importantly, the quality of life assessment in our patients using the Lester Cough Questionnaire, or LCQ, showed marked improvement with a statistically significant reduction at both the 54 and 108 milligram BID doses. The LCQ is a 21-point scale with three different domains, physical, social, and psychological. An increase in total score of 1.3 points is considered clinically meaningful. For the 54 milligram and 108 milligram BID doses, There was a statistically significant 3.7 and 3.4 point increase, respectively, P equals 0.01 for the total LCQ score at week six. These are strong results for a six-week study. The LCQ is meaningful in patients with IPF. In fact, a publication from the large U.S. Pulmonary Fibrosis Foundation Registry demonstrated that a worse quality of life, as measured by the LCQ, correlated with the risk of worse health outcomes, such as respiratory hospitalizations and mortality. One of our key focuses at Trevi is remaining patient-centric as we plan for development and commercialization. In a recent patient advisory board meeting, we reviewed the CORAL results to get patients' reactions. The two most important factors to patients when looking for a future cough treatment We're seeing improvements in cough frequency and severity and quality of life, similar to what we've heard from physicians. Several patients remarked that with the kind of change in cough seen in coral, it would be incredibly impactful and positive in their day-to-day lives. I was struck by how much cough controls patients' daily activities and how they isolate or compensate to avoid the embarrassment of coughing out in public. Coming off this data, Jim and his team have been very busy preparing for the end of Phase II FDA meeting and the next set of trials. We will provide more detailed guidance when we initiate each trial, but let me give you a brief update on the priorities over the next few months. First, we are currently conducting a couple of important Phase I studies. We are working on completing our title study, which is studying the respiratory function and safety of Hiduvio on IPF patients, as well as conducting a drug-drug interaction study looking at any potential PK effects of nalbufine when co-administered with perfenadone and nintenadib, both anti-fibrotics that are taken by patients with IPF and other progressive fibrotic diseases. We expect to have the data from both of these trials in time for our end-of-Phase II meeting with the FDA. 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 to gain alignment on the Phase III program for COFF and IPF, as well as any other NDA-enabling work which needs to be completed. In parallel, the team has been preparing to initiate the Phase III program in the first half of next year. We have also been preparing for a study in other non-IPF interstitial lung diseases. This population will include non-IPF patients that have lung fibrosis and 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 cough, and these patients are primarily seen by the same pulmonologist that see the IPF patients. This keeps our clinical and commercial efforts efficient and creates synergies. We plan to request a meeting with the FDA this year to discuss our study design for non-IPF-ILD and the protocol for this indication. Once we have FDA input, we will be prepared to initiate the study. Finally, we have been working on the next study in refractory chronic cough. We expect that to be a Phase IIb parallel arm study design, looking at dose ranging, and are planning to initiate that study in the first half of next year as well. So, as you can see, there's a lot of clinical development planning going on at Trevi, as well as preparation work to align with the regulatory authorities. This takes time to ensure that we get these next set of trials right. We will provide updates on next steps as we gain alignment and have line of sight to study starts. I will now turn it over to Lisa to review our financial results, and we will open it up for any questions you may have.

Thank you, Jennifer, and good afternoon, everyone. The full financial results for the three months ended June 30th, 2025 can be found in our press release issued ahead of this call and our 10Q which was filed with the SEC today after the market closed. For the second quarter of 2025, we reported a net loss of 12.3 million compared to a net loss of 12.4 million for the same quarter in 2024. R&D expenses decreased to 9.4 million during the second quarter of 2025 compared to 10 million in the same quarter in 2024. The reduction was primarily due to decreased costs related to our Phase 2A river trial, our human abuse potential study, and our Phase 2B coral trial, all of which were actively enrolling in the prior year. This was partially offset by increased costs related to our recently initiated Phase 1 drug-drug interaction study and personnel and related expenses. G&A expenses increased to 4.3 million during the second quarter of 2025 compared to 3.3 million in the same quarter of 2024. primarily due to an increase in professional fees and personnel and related expenses. The personnel and related expenses were primarily due to increased headcount. Approximately $500,000 of the $1 million increase in total general and administrative expenses was due to costs to prepare for SOC Section 404 related to our internal controls. These requirements become more rigorous as the company's market cap grows. As we continue our readiness efforts, we expect approximately this level of expense for the second half of 2025, and the expense may increase going forward. As of June 30, 2025, our cash and investments totaled approximately $204 million. As Jennifer mentioned, the increase in our cash and investments was primarily a result of the successful public offering we completed in June 2025 after the release of the data from our Phase 2b CORAL trial that resulted in gross proceeds of approximately 115 million, including the full exercise of the green shoe. Our cash and investment balance gives us cash runway into 2029 and enables us to fund two phase three trials of Hadoobio for the treatment of chronic cough in patients with IPF, our planned trial for chronic cough in patients with non-IPF ILD, our next trial in patients with RCC, the phase one work Jennifer discussed, and it enables pre-commercial planning activities. In summary, TREPI is in a strong position financially to execute our business plan. This concludes our prepared remarks. I will now turn the call back over to the operator for Q&A.