Trevi Therapeutics, Inc.

Good afternoon and welcome to the Trevi Therapeutics fourth quarter and year-end 2025 earnings conference call. At this time, all participants are in a listen-only mode. After today's presentation, there will be an opportunity to ask questions. To ask a question during the session, you will need to press star 1-1 on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star 1-1 again. Please be advised that today's conference 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 annual 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, even if its views change. I would now like to turn the conference call over to Jennifer Good, Trevi's president and CEO. Please go ahead.

Good afternoon, and thank you for joining us for our fourth quarter 2025 earnings call and business update. Joining me today on this call are my colleagues, Dr. James Casella, our chief development officer, Farrell Simon, our chief commercial officer, and David Hastings, our chief financial officer. I want to welcome Dave to his first official earnings call with Trevi. His experience has already been felt in the company and we feel very fortunate that we were able to add him to our leadership team at this important time of execution and growth. So welcome, Dave. I will make some comments on the business and Dave will make some brief financial remarks. Then the team is happy to answer any questions you may have. 2025 was a major inflection point for growth at Trevi. driven by our positive data readouts in both the CORAL trial in patients with idiopathic pulmonary fibrosis or IPF-related chronic cough, and the RIVER trial in patients with refractory chronic cough or RCC. As a result of these data, we were able to raise capital, setting us up nicely for the next round of trials for each of our indications. That momentum has carried into the early part of this year as we have been preparing to initiate the next set of clinical trials. This work recently culminated in a positive end to phase two meeting with the FDA for our IPF-related cough program. We believe the path forward for our registration trials is clear, and the team at Trevi has been moving aggressively to initiate our phase three program. Let me provide you with an update on where we stand in each of our chronic cough indications. Beginning with our lead indication of Heduvia for the treatment of IPF-related chronic cough. At our recently held end of phase two meeting with the FDA, we believe we gained overall alignment on the plan for the remaining development program and pathway to NDA. First, I want to share that the meeting was very collaborative and we were appreciative of the preparation and comments from the FDA, especially with all of the changes going on at the agency. We had constructive dialogue around each of our questions and left with a good understanding of the path forward. During our interaction, we confirm the primary endpoint using the objective cost monitor and discuss the proposed key secondary endpoints and the evaluation of these endpoints. Based on the FDA's input, the company plans to conduct two pivotal phase three clinical trials and obtained agreement on the remaining phase one clinical studies to support an NDA submission. The company plans to conduct these two phase three trials in parallel and is on track to initiate the clinical program. We plan to initiate the first trial in the second quarter of this year. This trial will be a global 52-week trial with a primary efficacy endpoint following 24 weeks of fixed dosing. We have planned for the trial to include approximately 300 patients. The second confirmatory phase three trial, which we expect to initiate in the second half of this year, will also be a global trial. with a primary efficacy endpoint at 12 weeks and is estimated to enroll approximately 130 patients. The two studies are almost identical in design, except for the different duration for the primary efficacy endpoints and sample sizes. The reason for these differences is the FDA interest in a 24-week readout to support durability of effect in at least one of the trials. As for the end of the trials, the 52-week trial with the 24-week endpoint is powered for all of the key secondary endpoints that we would hope to include in the label and supports an adequate safety database. The second phase three trial is studying a 12-week endpoint to confirm the primary efficacy outcomes, along with providing additional safety through 12 weeks of dosing. IPF-related chronic cough is a new indication for the FDA. And we believe this pivotal program provides robust safety and efficacy data for a potential NDA submission. In the US, there are approximately 150,000 IPF patients, two-thirds of which have uncontrolled chronic cough. These cough patients have a high unmet need with no FDA-approved therapies. With our distinct mechanism of action and known safety and tolerability profile, We believe we are well-positioned to have potentially the first therapy for the treatment of IPF-related chronic cough. Also, a quick comment on the remaining Phase I studies. These are all standard label-enabling studies, which we had already been planning for in our development program and were aligned with what we had submitted to the FDA in our briefing document. Jim can give more color in Q&A if you are interested. Following alignment with the FDA on our IPF-related chronic cough program, we now intend to submit a meeting request and protocol to the FDA to request our non-IPF interstitial lung disease or non-IPF-ILD-related chronic cough program. We intend to propose an adaptive Phase IIb trial to confirm dose and powering assumptions prior to rolling into one pivotal Phase III trial for approval. We are planning to file a supplemental NDA for this indication. We are planning to have this meeting in the third quarter of this year, and if all goes as planned with the FDA, initiate that trial by year end. This population will include non-IPF ILD patients who suffer from lung fibrosis and chronic cough. We estimate there are approximately 228,000 non-IPF ILD 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 pulmonologist that see IPF patients. This keeps our clinical and commercial efforts efficient and creates synergies. Finally, for refractory chronic cough, we are planning to conduct a Phase IIb parallel arm dose-ranging trial with three doses and placebo. The protocol is drafted and being submitted to regulatory authorities, and we have selected sites to conduct this trial. This trial is interesting scientifically as we explore whether dosing in RCC patients is lower or equivalent to doses we are testing in the IPF chronic cough trial. We plan to initiate this trial in the second quarter of this year as well and have included a sample size re-estimation readout when 50% of the patients complete the trial. It has been a busy time at Trevi preparing to launch this next round of clinical trials. Jim and his team have been working very hard to leverage the important learnings and relationships we have already built, as well as to expand our clinical footprint into the U.S. We are excited to initiate these trials and begin enrolling patients. Before I close, I want to note there will be two important meetings we are preparing for in the second quarter where we hope to see many of you. The first is an in-person Investor and Analyst Day on May 7th, from 10 a.m. to 12 p.m., followed by an optional lunch in New York City to discuss the company's clinical and commercial strategy. We will be joined by both IPF and RCC KOLs. At this event, we plan to lay out clinical trials and timelines in more detail, share recent commercial learnings that Ferrell has been busy at work on based on our recent data, hear from KOLs on their perspective, and I also plan to discuss our active efforts around obtaining additional intellectual property. So it should be an informative event. We will also webcast the event live for those of you that can't join us in person. Second, we will also be very active at the American Thoracic Society or ATS meeting this year with all of our submissions being accepted for either presentations or posters. We will be sharing some new data from our various trials at this meeting. We are planning on holding an investor event at ATS where Jim and Dr. Philip Molyneux, the lead investigator on our CORAL trial, will summarize and share the various data being presented at the conference. This meeting is being held in Orlando from May 17th to 19th, with our ATS investor event being held on Monday, May 18th. If you plan to attend ATS, please reach out to us as we would love to have you join us. So in closing, Trevi is well-positioned to execute against our plan of becoming the leader in chronic cough, providing therapy for these patients where there are not good options, and in the process, creating meaningful value for our shareholders. I will now turn it over to Dave for his remarks, and then we are happy to answer your questions. Dave?

Thanks, Jennifer, and good afternoon, everybody. First, I just want to say I'm thrilled to be participating in my first earnings call as CFO of Trevi. And before moving to the financial results, I want to take a moment to talk about why I took this role. The company has impressive clinical data and indications with high unmet medical need that offer a significant commercial opportunity. Importantly, given their specialty nature, we can commercially launch our indications effectively. In addition, the company has a proven track record of using its capital efficiently as it progresses its key clinical programs. Also, after meeting the team, I felt confident in their ability to execute, and I'm excited about the opportunity to contribute. Now turning to our key financial metrics, which are cash, our runway, and what that runway funds. We ended 2025 with approximately $188 million in cash, cash equivalents, and marketable securities, which gives us an expected runway into 2028. This runway allows us to provide top-line data in our key clinical trials. This includes our Phase IIb clinical trial in RCC, our Phase IIb clinical trial in non-IPF-related chronic cough, and importantly, top-line data in our 12-week pivotal Phase III clinical trial in IPF-related chronic cough. So while we're well-positioned from a cash runway perspective to reach key clinical milestones, It is important to ensure that Trevi is always appropriately capitalized given the key inflection points and significant clinical trial data readouts the company has in front of it. So with that, I'll now turn the call back over to the operator to open the call for Q&A. Operator? Thank you.