Trevi Therapeutics, Inc.

Good afternoon and welcome to the Trevi Therapeutics fourth quarter and year-end 2024 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 marks that management makes during this conference call about the company's future expectations, plans, and prospects constitute forward-looking statements for purposes of the state 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 over to Jennifer Good, Trevi's President and CEO. Please go ahead.

Good afternoon, and thank you for joining us for our fourth quarter and year-end 2024 Earnings Call and Business Update. Joining me today on this call is my colleague, Lisa Delfini, Trevi's Chief Financial Officer. Lisa and I will make some comments on the business and financial results, then we are happy to answer any questions that you may have. 2024 was a strong year of execution by Team Trevi, which delivered three positive data readouts over the past few months. The Human Abuse Potential Study, the Sample Size Reestimation, the CORAL Study in Chronic Cough Patients with IPF, and the RIVER study in patients with refractory chronic cough, or RCC. These trials in total were conducted across 11 countries in approximately 75 different sites and through multiple regulatory authorities. I am proud of our team and the urgency and commitment they had to running high-quality trials. Each of these trials had data analyses that were very important to advancing the clinical development plan of Hadovio. Let me briefly review each of these key readouts. In December, we read out positive results in our human abuse potential or HAP study. We needed to bring the package on drug likability up to current day standards since nalbufine is centrally acting therapy. As a reminder, injectable nalbufine, which is indicated for severe pain, has been around for decades and continues to be unscheduled by the DEA. Nalbufine belongs to a class of drugs known as mixed agonist antagonists that were designed for patients to get the efficacy of opioids but without the abuse potential. There are two primary reasons for nalbufine remaining unscheduled all these years. First, because of the new antagonism effect of the drug, which can elicit withdrawal symptoms in individuals who are abusing opiate class drugs, it is not preferred or sought after by these individuals. Second, in the DEA's ongoing surveillance, there are no significant issues of abuse detected. Both the 162 milligram and the 81 milligram nalbufine doses studied show statistically significant lower relative drug liking compared to butorphanol. Based on the effective doses that we are seeing in cough, it is likely that the 162 milligram dose fulfills the requirement of 3X, the marketed dose, to be considered supertherapeutic. There's nothing else we need to do until filing our NDA when we will submit an eight factor plan which will include this data. And a final determination on whether there will be changes in scheduling will be made upon approval by the FDA and DEA. We do not believe we've shown anything in our program that changes the abusability risk profile of this drug and that it will remain unscheduled. But that decision will ultimately be made later. Moving on to our clinical data. In December, we announced the results of the sample size re-estimation, or SSRE, analysis in our Phase 2b study in patients with IPF chronic cough. This was a pre-planned statistical look on the highest dose arm, 108 milligrams BID, when 50% of the originally planned patients completed the six weeks of treatment to confirm the original powering assumptions. The analysis was done by an unblinded statistician external to the company. The only information we received back was regarding whether a change to sample size was required. We were very pleased with the result that the SSRE confirmed the original sample size of 160 patients. This positive result essentially confirms the assumptions of effect size of the study, expected variability, and confirmed a conditional power at the 50% enrollment point of at least 80% or greater. This was exciting news for us and allowed us to stay on the original timelines for the study and wrap up enrollment in February of this year. Just a little color on enrollment. We had our biggest months of enrollment in December and January, which I think speaks to the excitement about a potential treatment and the significant unmet need in these IPF patients suffering from chronic cough. We currently have a handful of patients completing their treatment and expect to announce data from this trial in the second quarter of this year. This is our lead indication, and we are excited to get the data from this dose-ranging study and advance the development program. Finally, just last week, we announced the data from our Phase IIa River trial in patients with RCC, which includes those with unexplained chronic cough. RCC is a debilitating disease that affects approximately 2 to 3 million U.S. patients and has no approved therapies in the U.S. Importantly, there have been many drugs studied in this condition which have failed, all primarily peripherally acting agents with only one drug still in late stage development. Our hypothesis heading into the RIVER study was that our central and peripheral mechanism could change the outcome for patients that suffer with this disease. The types of chronic cough we are studying are linked through hypersensitivity at the brain and why we believe the central aspect of our mechanism is important. As reported last week, Heduvio met the primary endpoint in the RIVER study with a statistically significant reduction in 24-hour objective cough frequency, achieving a p-value of less than 0.0001 with a 57% placebo-adjusted change from baseline, and importantly, showed the same strong effect across a range of cough counts, including patients with moderate or severe cough. So, we are excited to progress development of Heduvio and RCC. As we have explained, with IPF as our lead indication and a specialty commercial sales model, we will develop Heduvio and RCC for patients which have failed prior therapy. We believe there are many patients not getting relief from the drugs currently being used off-label, and even if a P2X3 antagonist is approved, they have only been shown to work in the most severe coffers. which represents less than a third of the market. So there will still remain a high unmet need for RCC patients who have exhausted available treatment options. By moving to treatment failure patients in RCC, we focus on the patients with the highest unmet need, allowing us to target a subsegment of the RCC population and maintain our specialty IPF pricing. So data readouts at Trevi have been on a roll. Next up is our Phase IIb readout for the CORAL trial in IPF chronic cough patients. As I mentioned, we expect that data next quarter. The team has been busy planning for the next steps to quickly progress development of Hadovio in both IPF and RCC. The next key steps in development are for the IPF cough program, we will get the data, and assuming it is positive, we'll prepare for an end-of-Phase II meeting with the FDA. which we expect will happen by the end of 2025. At the meeting, we expect to discuss our planned pivotal program, study designs, and required safety database, as well as any other development studies we need to do for an NDA filing. For the RCC program, we are waiting on final data sets and developing a protocol for the next study. We will request a meeting with the FDA to get their input on our program and next study. We are planning on releasing more of the RIVER data at both the American Thoracic Society meeting in May in San Francisco, as well as the European Respiratory Society Congress meeting in September. As a side note, we are planning on being quite active at ATS in San Francisco in mid-May. So if any of you plan to attend, please let me know. We are planning on hosting a KOL panel featuring both IPF experts and an RCC doctor for investors. As you can see, we made a lot of progress this year and Heduvio is now the first and only therapy in clinical development to show a statistically significant reduction in chronic cough across patients with IPF and RCC. It positions Heduvio as a first in class therapy in IPF and potentially best in class across chronic cough indications. We have a focused plan on developing Heduvio in serious chronic cough conditions that our team can execute and we believe can generate significant value for the company and its shareholders. I will now turn it over to Lisa to review our financial results, then 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 and 12 months ended December 31st, 2024 can be found in our press release issued ahead of this call and our 10-K, which was filed with the SEC today after the market closed. For the fourth quarter of 2024, we reported a net loss of $11.4 million compared to a net loss of $7.8 million for the same quarter in 2023. R&D expenses were $9.3 million during the fourth quarter of 2024 compared to $6.5 million in the same quarter in 2023. The increase was primarily due to increased clinical trial costs in our Phase IIb choral trial, our Phase IIa river trial, and our HAP study, as well as an increase in personnel-related expenses. G&A expenses. increased to $2.9 million during the fourth quarter of 2024, compared to $2.4 million in the same period of 2023, primarily due to an increase in stock-based compensation and personnel-related expenses. As of December 31, 2024, our cash, cash equivalents, and marketable securities totaled $107.6 million. This included a $50 million unwritten offering we completed in December after the two positive data readouts that Jennifer discussed. This set us up nicely to not have to raise off of our positive RCC data last week. Our cash runway guidance into the second half of 2026 remains unchanged and funds completing our ongoing Phase IIb choral trials for chronic cough in patients with IPF, and based on our current estimates, our next RCC trial. It does not include funding for the next studies in IPF other than some startup costs. In 2025, we expect cash burn net of interest income of about 12 to 14 million per quarter in Q1 and Q2. Over the next couple quarters, we will be getting feedback from the FDA and planning the subsequent trial in RCC and assuming positive data trials in IPF and non-IPF ILDs. We will give additional cash burn guidance as we provide guidance on the design and start date for these trials. Our current fully diluted shares outstanding are approximately 137 million, which includes approximately 10 million stock options outstanding. This concludes our prepared remarks. I will now turn the call back over to the operator for Q&A.