Trevi Therapeutics, Inc.

Good afternoon and welcome to the Trevi Therapeutics first quarter 2024 earnings conference call. At this time, all participants will be in a 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 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 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 Goode, Trevi's President and CEO. Please go ahead.

Good afternoon, and thank you for joining us for our first quarter 2024 earnings call and business update. Joining me today on this call are my colleagues, Lisa Delfini, Trevi's Chief Financial Officer, and Dr. David Clark, Trevi's Chief Medical Officer. We reported Q4 earnings just six weeks ago, so Lisa and I will give a brief update, then the three of us are happy to answer any questions. This is a busy time at Trevi, advancing our clinical development plans for both refractory chronic cough, or RCC, as well as cough and idiopathic pulmonary fibrosis, or IPF. Let me provide a brief update on our various trials, beginning with our Phase IIa trial in RCC, which is expected to read out later this year. Refractory chronic cough, or RCC, is a debilitating disease that affects up to 10% of the adult population and is defined as a persistent cough lasting greater than eight weeks, despite treatment for the underlying condition. With a lack of any approved therapies for RCC in the U.S., there continues to be a significant unmet and urgent need for new potential therapies. The key point of differentiation for Heduvia in refractory chronic cough is the mechanism of action. which works synergistically both centrally in the brain and peripherally in the lungs. We believe Heduvia's mechanism has the potential to work in more patients and potentially have a stronger effect across a broader range of baseline cough counts than peripheral-only mechanisms like the P2X3 inhibitors. Our RCC trial, RIVER, is a Phase IIa double-blind randomized placebo-controlled two-period crossover study evaluating the reduction of cough in approximately 60 patients. This design is similar to other Phase 2A cough trials run to date, but does incorporate a meaningful difference. These patients will be randomized with a one-to-one stratification between those with 10 to 19 coughs per hour and those with greater than 20 coughs per hour. Each treatment period will last three weeks, separated by a three-week washout period. Patients on Heduvia will have the dose titrated weekly from 27 milligrams up to 108 milligrams twice daily across the dosing period. The primary efficacy endpoint is the relative change in the 24-hour cough frequency as measured by an objective cough monitor. The study will also explore secondary endpoints, including patient-reported outcome measures for cough and quality of life. We now have all 14 sites activated for this trial and see almost an even split in the enrolled subjects between each arm, the 10 to 19 and greater than 20 cough counts in the study. Enrollment is progressing and we continue to expect top-line data from this study in the second half of this year. Next, an update on our lead program in IPF chronic cough. IPF is a serious end-of-life disease. Chronic cough is reported by approximately 85% of patients suffering from IPF and has similar significant physical, psychological, and social impacts to that of RCC, but may also be a risk factor that plays a role in the progression of the underlying disease of IPF. The constant lung injury, micro tears, and potential inflammation caused by persistent coughing may lead to worse health outcomes for patients, such as increased respiratory hospitalizations, mortality, or need for transplant. With no currently approved treatment options for chronic cough and IPF, patients and providers have an urgent need for new therapies. While there are a lot of ongoing development programs in IPF, current and in-development therapies have not shown an impact on chronic cough, which is one of the most difficult aspects of IPF, elevating the unmet need. Our trial, CORAL, is a Phase IIb parallel-arm dose-ranging study that will study three active doses of Heduvia and placebo. The study is a six-week trial in approximately 160 patients. We are conducting this study in multiple countries and sites to be able to complete enrollment in a timely manner. We expect to have the majority of our planned 60 sites activated by the end of June. Enrollment is progressing and we are working with our sites to ensure our study is top of mind. We reaffirm our guidance for this study in which we expect to read out the results from our sample size re-estimation analysis in the second half of this year and we continue to expect top line data for the full study in the first half of 2025. As a reminder, the SSRE is conducted when 50% of the subjects complete the study. We intend to share the SSRE results once it is complete, which will either confirm our current study sizing assumptions recommend upsizing within a pre-specified range, or indicate futility. We have also made good enrollment progress on our human abuse potential study, or HAP, this year. This study is now approximately 75% enrolled, and we expect to complete enrollment this summer. The objective of this study is to determine the abuse potential of oral nalbufine relative to butorphanol and placebo, and was designed and agreed upon with FDA input. Recall that parenteral nalbufine is unscheduled by the DEA and was recently rereviewed by the DEA and left unscheduled. It's also important to note that the two parts of nalbufine's mechanism are also unscheduled, whether it be kappa agonists such as Corsuba or mu antagonists in products such as naloxone and naltrexone. This study will be submitted with our NDA as part of an eight-factor plan, which includes all the preclinical work done to date the mechanistic rationale for why this drug is unscheduled, our clinical data generated in our development programs, the results of this HAP study, as well as a public health rationale. Our goal is to have oral nalbuphenia remain unscheduled as the parental form has been all these years. We continue to expect top line data from this study in the second half of this year as well. Finally, our IND for IPF cough was cleared by the FDA And we expect to initiate our respiratory physiology study in the third quarter of 2024. We anticipate this study being conducted in the U.S. and in the U.K. The goal of this study is to systematically measure the impact of nalbuphener on respiratory depression in varying levels of disease severity and IPF to determine our phase three patient population. To date, we have excluded sleep disordered breathing patients in our studies and we want to better characterize the safety in this group as we move forward. As you can see, it is a busy time clinically for Trevi, and we believe the data from these trials will be important to inform the development path forward for Heduvia across chronic cough conditions. We are excited to begin completing these studies in the second half of this year and reporting the data. On a final note, our management team will be attending several medical conferences over the next few months, including the American Thoracic Society meeting in San Diego in a couple weeks, the London Cough Conference in July, and the European Respiratory Society meeting in Austria in September. Please let us know if you plan to attend, as we would love to meet with you. I will now turn it over to Lisa to review our financial results, then we will open it up for any questions.

Thank you, Jennifer, and good afternoon, everyone. The full financial results for the three months ended March 31st, 2024 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. The first quarter of 2024 was a quiet quarter for finance as the rest of the company is operationally focused on the enrollment and execution of our four trials that Jennifer discussed today. For the first quarter of 2024, we reported a net loss of $10.9 million compared to a net loss of $6.4 million for the same quarter in 2023. R&D expenses were $8.8 million during the first quarter of 2024 compared to $5 million in the same quarter of 2023, primarily due to increased clinical development expenses for our Phase IIb choral trial, our Phase IIa river trial, and our HAP trial. These increases were partially offset by decreased clinical development expenses for our Phase IIb-3 PRISM trial. G&A expenses were $3.1 million during the first quarter of 2024 compared to $2.6 million in the same period of 2023, primarily due to increases in information technology and finance staffing and activities as well as professional fees. Other income net was $1 million in the first quarter of 2024 compared to $1.2 million in the same period of 2023. As of March 31st, 2024, our cash, cash equivalents and marketable securities totaled $72.8 million compared to $83 million as of December 31st, 2023. We used about $10.9 million in cash in Q1-24, offset by about $700,000 of interest received. This is within the range of our expected cash burn for the year of $9 to $12 million per quarter. Our cash runway guidance remains unchanged, and we have cash, cash equivalents, and marketable securities into 2026. This concludes our prepared remarks, and I will now turn the call back over to the operator for Q&A.