Trevi Therapeutics, Inc.

Good afternoon, and welcome to the Trevi Therapeutics second 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 Act 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 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. I will give an update on the progress in our clinical trials, and Lisa will give a brief financial update. Then the three of us are happy to answer any questions that you may have. This has been a fun but busy quarter at Trevi as we continue to execute against our clinical development plans for both chronic cough and idiopathic pulmonary fibrosis, or IPS. as well as refractory chronic cough, or RCC. We have a number of data readouts expected by year-end and are hoping to build on the strong efficacy data we saw in our Phase IIa trial in IPF chronic cough. To support this fast pace and focus on execution, we continued to bolster our team and we're happy to announce in April the hire of Dr. Meg Guerin, who is key in progressing the clinical development of Camlipixent while at Bellis Health. Meg is overseeing our RIVER trial day-to-day and has already started looking ahead to planning for our next trial. She has been a great addition to the team. Let me provide a brief update on our clinical trials, beginning with our Phase IIa RIVER trial in RCC, which is expected to read out in the fourth quarter of this year. RCC is a debilitating disease that affects approximately 2 to 3 million U.S. adults and is defined as a persistent cough lasting greater than eight weeks despite treatment for an underlying condition or where no underlying condition exists. With a lack of any approved therapies for RCC in the U.S. and several drug candidate failures, there continues to be a significant unmet need and an urgency from patients and providers for new therapies. We believe our key point of differentiation for Heduvia is the mechanism of action, which works synergistically both centrally in the brain and peripherally in the lungs. We believe this mechanism has the potential to work more broadly in RCC patients and potentially have a stronger effect across the broader range of baseline cough counts than peripheral-only mechanisms. Our RCC trial is the standard phase 2a crossover design that has been conducted across several cough trials run to date and is planned to enroll approximately 60 patients. These patients will be randomized with a one-to-one stratification. or approximately 30 in each arm, between those with 10 to 19 coughs per hour, moderate cough, and those with greater than or equal to 20 coughs per hour, high cough. This trial has been progressing nicely, and we now have approximately 80% of the subjects enrolled. Based on the current run rate, we expect to report data from this study in the fourth quarter of this year. However, I want to note that we currently have an imbalance in the enrolled subjects between the two stratification arms, i.e., the 10 to 19 and greater than 20 cough counts. The enrollment between the two arms has fluctuated throughout the study. This is important data to inform future development, and there may be a scenario where we get to our overall planned N of 60, but keep the study open a little longer to balance the arms. We are excited to complete the enrollment of this study and report the data in this important chronic cough condition. 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 significant physical, psychological, and social impacts. Cough may also be a risk factor that plays a role in the progression of the underlying disease. The constant lung injury, micro tears, and inflammation caused by persistent coughing may lead to worse health outcomes for patients. With no currently approved treatment options for chronic cough and IPF, patients and providers have an urgent need for new therapies. Our IPF chronic cough trial, CORAL, is a Phase IIb parallel arm dose-ranging study that will investigate 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 now have the majority of our sites activated and enrollment is progressing nicely. We have great relationships with the investigators in the trial and are communicating with them frequently to ensure our study is top of mind. The next milestone in this study is to conduct a sample size re-estimation, SSRE analysis, when 50% of the patients complete. This analysis will be done by an unblinded statistician external to the company who will rerun the power calculations using actual data. We will get very limited information back, but we will be informed of one of the following three outcomes. One, continue on as planned with the current planned number of patients. reconfirming the original powering assumptions. Two, the drug is working within the pre-specified promising zone, but will require an upsize in the number of patients to maintain the power. Or three, the drug is not working in the pre-specified range and the company should consider stopping. We will announce the results of this analysis and we have the information, which we expect in the fourth quarter of this year. We continue to expect top line data for the full study in the first half of 2025, subject to the result of the SSRE. We also are conducting two important supportive studies this year, the Human Abuse Potential or HAP study, as well as the Respiratory Physiology study. I will give you a quick update on both. The HAP study is currently 95% enrolled and will require one more cohort of dosing to complete. We expect a complete enrollment and dosing in the third quarter with data from this study reported in the fourth quarter. Finally, we have initiated a phase one respiratory physiology study, which is being conducted to systematically measure respiratory function in varying levels of disease severity and IPF to help determine our phase three patient population. To date, we have excluded sleep disordered breathing patients in our clinical studies and we want to better characterize the safety overall in the patient population. The protocol has been approved in both the US and the UK, and the study has initiated patient screening. We expect to enroll approximately 25 patients that will be inpatient for 10 days. The primary endpoint of the trial is the effect of escalating doses of Heduvia on respiratory function as measured by minute ventilation. Secondary endpoint measures of additional respiratory functions are also included. As you can see, these studies have progressed nicely and data from these trials will be important to inform the development path forward for Hadovio in chronic cough conditions. I want to thank our team who have worked hard to keep the enrollment on plan. We look forward to completing these clinical trials and reporting out the data beginning in the fourth quarter of this year. 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 months ended June 30th, 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. For the second quarter of 2024, we reported a net loss of 12.4 million compared to a net loss of 7.1 million for the same quarter in 2023. R&D expenses were 10 million during the second quarter of 2024 compared to 5.8 million in the same quarter in 2023, which reflects the strong clinical activity across all four of our trials. DNA expenses were 3.3 million during the second quarter of 2024 compared to 2.5 million in the same period of 2023. primarily due to increases in personnel and related expenses, market research costs, and information technology services. As of June 30, 2024, our cash, cash equivalents, and marketable securities totaled $69.5 million compared to $83 million as of December 31, 2023. During the quarter, we issued approximately 1.5 million shares from our ATM, which was purchased by a single buyer. This cash inflow strengthens our runway post-data readouts on our current clinical trials. We continue to expect that our cash burn, excluding the proceeds from the share issuance, will average $9 to $12 million per quarter in 2024, and we will have cash runway into 2026. This concludes our prepared remarks. I will now turn the call back over to the operator for Q&A.